<SEC-DOCUMENT>0000874015-25-000089.txt : 20250219
<SEC-HEADER>0000874015-25-000089.hdr.sgml : 20250219
<ACCEPTANCE-DATETIME>20250219160639
ACCESSION NUMBER:		0000874015-25-000089
CONFORMED SUBMISSION TYPE:	10-K
PUBLIC DOCUMENT COUNT:		110
CONFORMED PERIOD OF REPORT:	20241231
FILED AS OF DATE:		20250219
DATE AS OF CHANGE:		20250219

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			IONIS PHARMACEUTICALS INC
		CENTRAL INDEX KEY:			0000874015
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		ORGANIZATION NAME:           	03 Life Sciences
		IRS NUMBER:				330336973
		STATE OF INCORPORATION:			CA
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		10-K
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		25639940

	BUSINESS ADDRESS:	
		STREET 1:		2855 GAZELLE COURT
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92010
		BUSINESS PHONE:		7609319200

	MAIL ADDRESS:	
		STREET 1:		2855 GAZELLE COURT
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92010

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	ISIS PHARMACEUTICALS INC
		DATE OF NAME CHANGE:	19930328
</SEC-HEADER>
<DOCUMENT>
<TYPE>10-K
<SEQUENCE>1
<FILENAME>form10k.htm
<DESCRIPTION>IONIS PHARMACEUTICALS, INC. 10-K 12-31-2024
<TEXT>
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<div>UNITED STATES</div>
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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="dei:CityAreaCode" id="Fact_caca5816e59f4d42a8a7d9f3a660ec40" contextRef="c20240101to20241231">760</ix:nonNumeric>-<ix:nonNumeric name="dei:LocalPhoneNumber" id="Fact_bc81b0ba10ac4ef1ae22ab217761d4bd" contextRef="c20240101to20241231">931-9200</ix:nonNumeric></div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Registrant&#8217;s telephone number, including area code)</div>

  <div><br/>
  </div>

  <div style="text-align: center; margin-top: 6pt; margin-bottom: 6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Securities registered pursuant to Section 12(b) of the Act:</div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 39.77%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Title of each class</div>
        </td>

    <td style="width: 1.82%; vertical-align: top;">&#160;</td>

    <td style="width: 15.83%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Trading symbol</div>
        </td>

    <td style="width: 1.39%; vertical-align: bottom;">&#160;</td>

    <td style="width: 41.19%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Name of each exchange on which registered</div>
        </td>

  </tr>

  <tr>

    <td style="width: 39.77%; vertical-align: top; border-top: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:Security12bTitle" id="Fact_539a725081e1431e978878cd5f2facb6" contextRef="c20240101to20241231">Common Stock, $.001 Par Value</ix:nonNumeric></div>
        </td>

    <td style="width: 1.82%; vertical-align: top;">&#160;</td>

    <td style="width: 15.83%; vertical-align: top; border-top: #000000 2px solid;">
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        </td>

    <td style="width: 1.39%; vertical-align: top;">&#160;</td>

    <td style="width: 41.19%; vertical-align: top; border-top: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The <ix:nonNumeric name="dei:SecurityExchangeName" id="Fact_c68ec858a453414ea9f513d7bb7d7d68" contextRef="c20240101to20241231" format="ixt-sec:exchnameen">Nasdaq</ix:nonNumeric> Stock Market LLC</div>
        </td>

  </tr>


</table>
  <div style="text-align: left; text-indent: 18pt;"><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Securities registered pursuant to Section 12(g) of the Act: <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">None</span></div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 32.84%; vertical-align: top;">&#160;</td>

    <td style="width: 34.31%; vertical-align: top; border-bottom: #000000 2px solid;">&#160;</td>

    <td style="width: 32.84%; vertical-align: top;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. <ix:nonNumeric name="dei:EntityWellKnownSeasonedIssuer" id="Fact_53c49ad1ac384529819bcf90b059ed6a" contextRef="c20240101to20241231">Yes</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;&#160; </span>No <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check if the Registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;&#160; </span><ix:nonNumeric name="dei:EntityVoluntaryFilers" id="Fact_4eb5aaff9b7a4dd4bb04a7313365fbc6" contextRef="c20240101to20241231">No</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the Registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934
    during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. <ix:nonNumeric name="dei:EntityCurrentReportingStatus" id="Fact_0548376ddde84726b48299ac46181663" contextRef="c20240101to20241231">Yes</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;&#160; </span>No <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of
    Regulation S-T (&#167;232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). <ix:nonNumeric name="dei:EntityInteractiveDataCurrent" id="Fact_67ffaa98641a4ed2ae627af781a78c9b" contextRef="c20240101to20241231">Yes</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;&#160; </span>No <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

  <div style="text-align: left;"><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an
    emerging growth company. See the definitions of &#8220;large accelerated filer,&#8221; &#8220;accelerated filer,&#8221; &#8220;smaller reporting company,&#8221; and &#8220;emerging growth company&#8221; in Rule 12b-2 of the Exchange Act.</div>

  <div style="text-align: center;"><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 48.93%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:EntityFilerCategory" id="Fact_c983def5970a4a3186548a7677ed2316" contextRef="c20240101to20241231">Large Accelerated Filer</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;</span></div>
        </td>

    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>

    <td style="width: 48.93%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accelerated Filer <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 48.93%; vertical-align: top;">&#160;</td>

    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>

    <td style="width: 48.93%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 48.93%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-accelerated Filer <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>
        </td>

    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>

    <td style="width: 48.93%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Smaller Reporting Company <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';"><ix:nonNumeric name="dei:EntitySmallBusiness" id="Fact_a4f9a244978047728caf18fddcb82758" contextRef="c20240101to20241231" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 48.93%; vertical-align: top;">&#160;</td>

    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>

    <td style="width: 48.93%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Emerging Growth Company <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';"><ix:nonNumeric name="dei:EntityEmergingGrowthCompany" id="Fact_d7b1681af4614ee89ccda637ab59a97d" contextRef="c20240101to20241231" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></span></div>
        </td>

  </tr>


</table>
  <div style="text-align: center;"><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If an emerging growth company, indicate by check mark if the registrant has
      elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. </span><span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant has filed a report on and attestation to its management assessment of the effectiveness of its internal
    controls over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';"><ix:nonNumeric name="dei:IcfrAuditorAttestationFlag" id="Fact_e8c0d709c956479aa2b0e019606d6a48" contextRef="c20240101to20241231" format="ixt-sec:boolballotbox">&#9746;</ix:nonNumeric></span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the
    filing reflect the correction of an error to previously issued financial statements.&#160; <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';"><ix:nonNumeric name="dei:DocumentFinStmtErrorCorrectionFlag" id="Fact_4939637cb11d4d23900c3746547cea5f" contextRef="c20240101to20241231" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by
    any of the registrant&#8217;s executive officers during the relevant recovery period pursuant to &#167;240.10D-1(b).&#160; <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Indicate by check mark whether the Registrant is a shell company (as defined in
      Rule 12b-2 of the Act). Yes </span><span style="font-size: 10pt; font-family: 'Segoe UI Symbol';"><ix:nonNumeric name="dei:EntityShellCompany" id="Fact_56df688880124998a2174e3648c29826" contextRef="c20240101to20241231" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></span><span style="font-size: 12pt; font-family: 'Segoe UI Symbol';">&#160; </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">No </span><span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The approximate aggregate market value of the voting common stock held by non-affiliates of the Registrant, based upon the last sale price of the common
    stock reported on The Nasdaq Global Select Market was $<ix:nonFraction name="dei:EntityPublicFloat" id="Fact_a9780b7a4ad04a4cb41b5cf43eb58514" contextRef="c20240630" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">5,738,934,243</ix:nonFraction> as of June 30, 2024.*</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The number of shares of voting common stock outstanding as of February 13, 2025 was <ix:nonFraction name="dei:EntityCommonStockSharesOutstanding" id="Fact_dec00a9664b3474c97b195e195feafc7" contextRef="c20250213" unitRef="U002" decimals="INF" scale="0" format="ixt:num-dot-decimal">158,964,772</ix:nonFraction>.</div>

  <div><br/>
  </div>

  <div style="text-align: center; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">DOCUMENTS INCORPORATED BY REFERENCE</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Portions of the Registrant&#8217;s definitive Proxy Statement to be filed on or about April 25, 2025 with the Securities and Exchange Commission in connection with the Registrant&#8217;s annual meeting of stockholders to be held on June 5, 2025 are incorporated by reference into Part III of this Report.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Excludes 25,611,183 shares of common stock held by directors and officers and by stockholders whose beneficial ownership is known by the Registrant to exceed 10 percent
            of the common stock outstanding at June 30, 2024. Exclusion of shares held by any person should not be construed to indicate that such
            person possesses the power, direct or indirect, to direct or cause the direction of the management or policies of the Registrant, or that such person is controlled by or under common control with the Registrant.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;">
    <hr style="border: none; border-bottom: 4px solid black; border-top: 1px solid black; height: 10px; color: #ffffff; background-color: #ffffff; text-align: center; margin-left: auto; margin-right: auto;"/></div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter" style="width: 100%;"></div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader" style="width: 100%;"></div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FORWARD-LOOKING STATEMENTS</div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><!--PROfilePageNumberReset%Num%4%%%--></div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">This report on Form 10-K and the information incorporated herein by reference includes forward-looking statements
    regarding our business and the therapeutic and commercial potential of our commercial medicines, additional medicines in development and technologies. Any statement describing our goals, expectations, financial or other projections, intentions or
    beliefs, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties and particularly those inherent in the process of discovering, developing and commercializing
    medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Our forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause
    our results to differ materially from those expressed or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those discussed in this report on Form 10-K, including
    those identified in Item 1A, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk Factors</span>. Although our forward-looking statements reflect the good faith judgment of our management, these
    statements are based only on facts and factors currently known by us. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking
    statements.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In this report, unless the context requires otherwise, &#8220;Ionis,&#8221; the &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221; refers to Ionis Pharmaceuticals, Inc.
    and its subsidiaries.</div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Summary of Risk Factors</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are a number of risks related to our business and our securities. Below is a summary of material factors that make an investment in
    our securities speculative or risky. Importantly, this summary does not address all of the risks that we face. Additional discussion of the risks summarized in this risk factor summary, as well as other risks that we face, can be found in this report
    on Form 10-K in Item 1A, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk Factors</span>:</div>

  <div style="text-align: left;"><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to generate substantial revenue from the sale of our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The availability of adequate coverage and payment rates for our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our and our partners&#8217; ability to compete effectively;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to successfully manufacture our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to successfully develop and obtain marketing approvals for our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to secure and maintain effective corporate partnerships;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to sustain cash flows and achieve consistent profitability;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to protect our intellectual property;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to maintain the effectiveness of our personnel;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The impacts of health epidemics, climate change, war and other global events; and</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our dependence upon our own and third-party information technology systems.</div>
        </td>

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  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">TRADEMARKS</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8220;Ionis,&#8221; the Ionis logo, and other trademarks or service marks of Ionis Pharmaceuticals, Inc. appearing in this report are the property of
    Ionis Pharmaceuticals, Inc. &#8220;Akcea,&#8221; the Akcea logo, and other trademarks or service marks of Akcea Therapeutics, Inc. appearing in this report are the property of Akcea Therapeutics, Inc., Ionis&#8217; wholly owned subsidiary. This report contains
    additional trade names, trademarks and service marks of others, which are the property of their respective owners. Solely for convenience, trademarks and trade names referred to in this report may appear without the &#174; or TM symbols.</div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CORPORATE INFORMATION</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporated in California in 1989 and in January 1991 we changed our state of incorporation to Delaware. In December 2015, we changed
    our name to Ionis Pharmaceuticals, Inc. from Isis Pharmaceuticals, Inc. Our principal offices are in Carlsbad, California.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We make available, free of charge, on our website, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">www.ionis.com</span>, our reports on Forms 10-K, 10-Q, 8-K and amendments thereto, as soon as reasonably practicable after we file such materials with, or furnish such materials to, the Securities and Exchange Commission, or SEC.
    Periodically, we provide updates about the company in the Newsroom section of the Investors &amp; Media page of our website. Any information that we include on or link to our website is not a part of this report or any registration statement that
    incorporates this report by reference. The SEC maintains an internet site, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">www.sec.gov</span>, that contains reports, proxy and information statements,
    and other information that we file electronically with the SEC.</div>

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  <div style="text-align: left;"><a id="TOC"><!--Anchor--></a><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FORM 10-K</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">For the Fiscal Year Ended December 31, 2024</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Table of Contents</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 10.51%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a href="#PARTI"><span style="text-decoration: underline;">PART I</span></a></div>
        </td>

    <td style="width: 83.22%; vertical-align: top;">&#160;</td>

    <td style="width: 6.27%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 10.51%; vertical-align: top;">&#160;</td>

    <td style="width: 83.22%; vertical-align: top;">&#160;</td>

    <td style="width: 6.27%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Page</div>
        </td>

  </tr>

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    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 1.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Business</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
        </td>

  </tr>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 1A.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item1A" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk Factors</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 1B.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item1B" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unresolved Staff Comments</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 1C.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item1C" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cybersecurity</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 2.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item2">Properties</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 3.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Legal Proceedings</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 4.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item4" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mine Safety Disclosures</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a href="#PARTII" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">PART II</a></div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 5.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Market for Registrant&#8217;s Common Equity, Related Stockholder
              Matters and Issuer Purchases of Equity Securities</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 6.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item6">Reserved</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 7.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Management&#8217;s Discussion and Analysis of Financial Condition and
              Results of Operations</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 7A.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item7A" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Quantitative and Qualitative Disclosures About Market Risk</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 8.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial Statements and Supplementary Data</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 9.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Changes in and Disagreements With Accountants on Accounting and
              Financial Disclosure</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 9A.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item9A" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Controls and Procedures</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 9B.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item9B" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other Information</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 9C.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item9C" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Disclosure Regarding Foreign Jurisdictions that Prevent
              Inspections</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

  </tr>

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    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a href="#PARTIII" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">PART III</a></div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

  </tr>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

  </tr>

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    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 10.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item10" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Directors, Executive Officers and Corporate Governance</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 11.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item11" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Compensation</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 12.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item12" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Security Ownership of Certain Beneficial Owners and Management
              and Related Stockholder Matters</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item13" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certain Relationships and Related Transactions, and Director
              Independence</a></div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item14" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Principal Accountant Fees and Services</a></div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a href="#PARTIV" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">PART IV</a></div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item15" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exhibits, Financial Statement Schedules</a></div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Signatures" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Signatures</a></div>
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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART I<a id="PARTI"><!--Anchor--></a></div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item1"><!--Anchor--></a>Item 1. Business</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Overview</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For three decades, we have invented medicines that bring better futures to people with serious diseases. As a pioneer in RNA-targeted
    medicines with a deep understanding of disease biology and an industry-leading drug discovery technology, we are driven to deliver innovative, life-changing advances for patients.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the last year, we delivered on our strategy to create accelerating value for all our stakeholders. With our commercial launch of
    TRYNGOLZA (olezarsen) in the United States, or U.S., following its approval by the U.S. Food and Drug Administration, or FDA, we began a new chapter as a fully integrated commercial-stage biotechnology company. We currently have six marketed medicines
    to treat serious diseases: TRYNGOLZA, WAINUA (eplontersen), SPINRAZA (nusinersen), QALSODY (tofersen), TEGSEDI (inotersen) and WAYLIVRA (volanesorsen).</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Marketed Medicines</div>

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            <div style="text-align: justify; margin-bottom: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TRYNGOLZA is approved in the U.S. as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia
              syndrome, or FCS. TRYNGOLZA is the first-ever FDA-approved treatment that significantly and substantially reduces triglyceride levels in adults with FCS and provides clinically meaningful reduction in acute pancreatitis, or AP, events when
              used with an appropriate diet (&#8804;20 grams of fat per day). TRYNGOLZA is the first medicine we are commercializing independently in the U.S.</div>
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            <div style="text-align: justify; margin-bottom: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA is approved in numerous countries, including the U.S. and United Kingdom, or UK, for the treatment of the
              polyneuropathy of hereditary transthyretin-medicated amyloidosis, or ATTRv-PN, in adults. WAINUA is the only approved medicine for the treatment of ATTRv-PN that can be self-administered via an auto-injector. We and AstraZeneca are
              co-developing WAINUA globally and co-commercializing WAINUA in the U.S. AstraZeneca has exclusive rights to commercialize WAINUA outside of the U.S.</div>
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            <div style="text-align: justify; margin-bottom: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA is a global market leader for the treatment of pediatric and adult patients with spinal muscular atrophy, or SMA. Our
              partner, Biogen, is responsible for commercializing SPINRAZA worldwide.</div>
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            <div style="text-align: justify; margin-bottom: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">QALSODY is approved in the U.S., European Union, or EU, China and Japan for the treatment of Amyotrophic Lateral Sclerosis, or
              ALS, in adults who have a mutation in the superoxide dismutase 1, or SOD1, gene, or SOD1-ALS. QALSODY received accelerated approval from the FDA and marketing authorization under exceptional circumstances from the European Medicines Agency,
              or EMA. QALSODY was the first treatment approved to target a genetic cause of ALS. Our partner, Biogen, is responsible for commercializing QALSODY worldwide.</div>
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            <div style="text-align: justify; margin-bottom: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI is approved in the EU, Canada and Brazil for the treatment of ATTRv-PN in adults. We currently sell TEGSEDI in Europe
              through our distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. We and Sobi terminated our agreement for TEGSEDI in North America, after which we discontinued TEGSEDI in North America. In Latin America, PTC Therapeutics
              International Limited, or PTC, is commercializing TEGSEDI in Brazil and is pursuing access in additional Latin American countries through its exclusive license agreement with us.</div>
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            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">WAYLIVRA is approved in the EU and Brazil </span>as an adjunct to
              diet in adult patients with genetically confirmed FCS and at high risk for acute, potentially fatal pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate. We sell WAYLIVRA in Europe through our
              distribution agreement with Sobi. In Latin America, PTC is commercializing WAYLIVRA in Brazil for two indications, FCS and familial partial lipodystrophy, or FPL, and is pursuing access in additional Latin American countries through its
              exclusive license agreement with us.</div>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In addition to our currently marketed medicines, we are also
      positioned to deliver multiple products to the market independently in the next three years. Donidalorsen for the treatment of hereditary angioedema, or HAE, is currently under regulatory review in the U.S., positioning us for our second independent
      commercial launch in 2025. We also have a rich innovative late- and mid-stage pipeline across our focus areas of neurology, cardiology and select areas of high patient needs. We currently have nine medicines in Phase 3 development and multiple
      additional medicines in early and mid-stage development. We delivered eight positive data readouts in the last year from our late- and mid-stage pipeline, including positive data for TRYNGOLZA, donidalorsen and ION582, our medicine for people with
      Angelman syndrome, or AS. And we further advanced our next-generation technologies for RNA-targeted medicines, including advancing our first program using our </span>mesyl phosphoramidate, or<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> MsPA, backbone into clinical development.</span></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earned revenues of $705
    million in 2024 and ended 2024 with a cash and short-term investment balance of $2.3 billion that enables our continued investments to support
    ongoing and upcoming planned launches and to advance our wholly owned medicines in development. Our key recent achievements, combined with our independent and partnered product launches anticipated over the next three years, position us well to help
    millions of patients with serious diseases and deliver increasing product and royalty revenue.</div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Our Marketed Medicines &#8211; Bringing Value to Patients Today</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">TRYNGOLZA (apoC-III)</span><sub style="font-weight: bold;">&#160;</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8211; </span>TRYNGOLZA (olezarsen), injection is an <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">APOC-III</span>-directed antisense medicine indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome, or FCS. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TRYNGOLZA lowers the body&#8217;s production of apolipoprotein C-III, or apoC-III, a protein produced in the liver that is a key regulator of triglyceride metabolism. TRYNGOLZA was approved by the FDA in December 2024 and is the first-ever
      FDA-approved treatment that significantly and substantially reduces triglyceride levels in adults with FCS and provides clinically meaningful reduction in AP events when used with an appropriate diet (&#8804;20 grams of fat per day). TRYNGOLZA is currently
      under regulatory review in the EU.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">FCS is a rare, genetic, potentially life-threatening form of sHTG that prevents the body from breaking down fats and severely impairs
    the body&#8217;s ability to remove triglycerides from the bloodstream due to an impaired function of the enzyme lipoprotein lipase, or LPL. While healthy levels for adults are below 150 mg/dL, people with FCS often have triglyceride levels of more than 880
    mg/dL and often have a history of pancreatitis. Those living with FCS have a high risk of potentially fatal AP, which is a painful inflammation of the pancreas, and chronic health issues such as fatigue and severe, recurrent abdominal pain. People
    living with FCS can also experience psychological and financial stress, which can significantly impact their quality of life. FCS is estimated to impact up to approximately 3,000 people in the U.S., the vast majority of whom remain undiagnosed.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also developing olezarsen to treat severe hypertriglyceridemia, or sHTG. See the &#8220;olezarsen&#8221; description under the section
    titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Our Innovative Late-Stage Pipeline of Ionis-Owned Investigational Medicines</span>, below for further information on our development program for
    sHTG.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">FDA approval was based on positive data from the placebo-controlled Phase 3 Balance study in adult patients with genetically identified
    FCS and fasting triglyceride levels &#8805;880 mg/dL. In the Balance study, TRYNGOLZA demonstrated a statistically significant reduction in triglyceride levels. TRYNGOLZA also demonstrated a substantial, clinically meaningful reduction in AP events. In
    addition, TRYNGOLZA demonstrated a favorable safety and tolerability profile in the Balance study.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TRYNGOLZA was reviewed by the FDA under Priority Review and had previously been granted Fast Track, Orphan Drug and Breakthrough Therapy
    designations for the treatment of FCS.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">WAINUA (TTR) &#8211; </span>WAINUA
    (eplontersen) injection is a transthyretin-directed antisense oligonucleotide indicated for the treatment of the polyneuropathy of hereditary transthyretin-medicated amyloidosis, or ATTRv-PN, in adults. WAINUA causes degradation of mutant and wild-type
    TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues. WAINUA was approved in the U.S. in December 2023 and was recommended for approval by the CHMP in the EU in October 2024.
    WAINUA is also approved in other markets, including the UK and Canada, with additional regulatory reviews underway. We and AstraZeneca are co-commercializing WAINUA in the U.S. and AstraZeneca has exclusive rest of world commercialization rights.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without
    treatment, is generally fatal within a decade. ATTR is caused by the accumulation of liver-derived misfolded TTR protein in tissues, such as the heart and the peripheral nerves, causing organ damage and failure. ATTR then causes complications, leading
    to cardiovascular, neurological and renal diseases such as heart failure and chronic kidney disease. There are both hereditary (ATTRv) and non-hereditary (wild-type) forms of ATTR. ATTR has several phenotypes including ATTR-cardiomyopathy, or ATTR-CM,
    which predominantly impacts the heart, potentially leading to heart failure, and ATTR-polyneuropathy, which predominantly affects the peripheral nervous system and mixed phenotype, where patients experience symptoms of both. Worldwide, there are an
    estimated 10,000 &#8211; 40,000 patients with ATTRv-PN. See the &#8220;Eplontersen&#8221; description under the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Our Innovative Late-Stage Pipeline of
      Partnered Investigational Medicines</span>, below for further information on our development program for ATTR-CM.</div>

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    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">FDA approval was based on the interim analysis of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">open-label







      </span>Phase 3 NEURO-TTRansform study in patients with ATTRv-PN. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The study compared WAINUA to the historical placebo arm from the TEGSEDI (inotersen) NEURO-TTR Phase 3
        study. </span>In the interim analysis, WAINUA demonstrated a statistically significant and clinically meaningful change from baseline for the co-primary endpoints of serum TTR concentration and Neuropathy Impairment Score +7, or mNIS+7.
      Additionally, WAINUA demonstrated a favorable safety and tolerability profile in the NEURO-TTRansform study.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA granted Orphan Drug designation to WAINUA for the treatment of ATTR.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">SPINRAZA (SMN) </span>&#8211; SPINRAZA
    (nusinersen) injection for intrathecal use is a survival motor neuron-2, or SMN2, directed antisense medicine indicated for the treatment of <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SMA </span>in pediatric and
    adult patients. SPINRAZA targets the root cause of SMA by increasing the production of functional survival motor neuron, or SMN, protein. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA is a global market leader
      for the treatment of patients with </span>SMA<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Our partner, Biogen, is responsible for commercializing SPINRAZA worldwide.</span></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SMA is characterized by loss of motor neu<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">rons in the spinal
      cord and lower brain stem. People with SMA have a deletion or defect in their </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SMN1</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> gene and rely on their </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SMN2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> gene to
      produce functional SMN protein, which motor neurons need to maintain motor function and muscle strength. However, in untreated people the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SMN2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> gene can only produce approximately 10% of the SMN protein critical for motor neurons, resulting in severe and progressive loss of motor function and strength. The rate and
      severity of degeneration varies depending on the amount of functional SMN protein a patient can produce. Type 1, or infantile-onset, SMA is the most severe form of the disease. Type 1 SMA patients produce very little SMN protein and often progress to
      death or permanent ventilation by the age of 2. Patients with Type 2 or Type 3, or later-onset, SMA produce more SMN protein, but also suffer from a progressive loss of muscle strength and function and a reduced life expectancy.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The approval of SPINRAZA was based on efficacy and safety data from multiple clinical studies, including two randomized,
    placebo-controlled Phase 3 studies, ENDEAR, in patients with infantile-onset SMA, and CHERISH, in patients with later-onset SMA as well as from SHINE, an OLE study for patients with SMA who participated in prior SPINRAZA studies. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, Biogen conducted the Phase 2 NURTURE study, an open-label study investigating the benefit of SPINRAZA when administered before symptom onset in patients genetically
      diagnosed with SMA which showed that early and sustained treatment with SPINRAZA helped participants to maintain and/or make progressive gains in motor function with most children achieving motor milestones within age-appropriate timelines and no
      major motor milestones were lost. SPINRAZA </span>demonstrated a favorable safety and tolerability profile in the studies.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen continues to expand the body of evidence supporting SPINRAZA&#8217;s durable efficacy and well-established safety profile to address
    the remaining needs of SMA patients of all ages through additional studies. These include the Phase 2/3 DEVOTE study, which evaluated a higher dose of SPINRAZA compared to the currently approved dose, the Phase 4 RESPOND study, evaluating the benefit
    of SPINRAZA in infants and children with a suboptimal clinical response to the gene therapy, onasemnogene abeparvovec and the Phase 3b ASCEND study evaluating the clinical outcomes and assessing the safety of a higher dose of SPINRAZA in children,
    teens and adults with later-onset SMA following treatment with risdiplam. The positive data generated from the DEVOTE study were the basis of the recent U.S. and EU regulatory submissions that were accepted for review for higher dose nusinersen.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">QALSODY (SOD1) &#8211; </span>QALSODY
    (tofersen) <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">injection for intrathecal use </span>is an antisense medicine indicated for the treatment of Amyotrophic Lateral Sclerosis, or ALS, in adults who have a mutation
    in the superoxide dismutase 1, or SOD1, gene, or SOD1-ALS. QALSODY inhibits the production of SOD1. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">QALSODY was </span>granted accelerated approval in April 2023 based on
    reduction in plasma neurofilament light chain, or NfL, observed in patients treated with QALSODY. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> In May 2024, QALSODY was also approved in the EU under exceptional circumstances. Additionally, QALSODY was recently approved in China and Japan. Our partner, Biogen, is responsible for commercializing
      QALSODY worldwide.</span></div>

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  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SOD1-<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ALS is a rare, fatal, neurodegenerative disorder
        caused by a mutation in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SOD1</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> gene leading to a
        progressive loss of motor neurons. As a result, people with SOD1-ALS experience increasing muscle weakness, loss of movement, difficulty breathing and swallowing and eventually succumb to the disease. Mutations in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SOD1</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> gene are responsible for approximately 2% of the estimated 168,000
        people who have ALS globally (SOD1-ALS). More than 15% of people with ALS are thought to have a genetic form of the disease; however, they may not have a known family history of the disease.</span></div>

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    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen is also evaluating tofersen for treatment of <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">presymptomatic







        individuals who have a SOD1 genetic mutation</span>.</div>

  </div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The QALSODY regulatory submissions included results from a
      Phase 1 study in healthy volunteers, a Phase 1/2 study evaluating ascending dose levels, the Phase 3 VALOR study, and the Phase 3 OLE study, as well as 12-month integrated results from the Phase 3 VALOR study and the Phase 3 open-label extension, or
      OLE, study. The 12-month integrated data show that earlier initiation of QALSODY, compared to delayed initiation, slowed declines in clinical function, respiratory function, muscle strength and quality of life and build on the results previously
      observed in the initial readout. The 12-month data compare patients with early initiation of QALSODY (at the start of VALOR) to those who had a delayed initiation of QALSODY (six months later, in the OLE). </span>Additionally, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">QALSODY demonstrated a favorable safety and tolerability profile in the VALOR study.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA and EMA granted QALSODY Orphan Drug designation for the treatment of ALS.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">TEGSEDI (TTR) &#8211; </span>TEGSEDI
    (inotersen) injection is a transthyretin-directed antisense oligonucleotide medicine indicated for the treatment of ATTRv-PN in adults. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI prevents the production of TTR
      protein, reducing the amount of amyloid buildup that damages organs and tissues. We currently sell TEGSEDI in Europe through our distribution agreement with Sobi. In Latin America, PTC is commercializing TEGSEDI in Brazil and is pursuing access in
      additional Latin American countries through its exclusive license agreement with us.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The approvals of TEGSEDI were based on efficacy and safety data from the Phase 3 NEURO-TTR study in patients with ATTRv-PN.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">WAYLIVRA (apoC-III) &#8211; </span>WAYLIVRA
    (volanesorsen) injection is an antisense oligonucleotide medicine indicated as an adjunct to diet in adult patients with genetically confirmed FCS and at high risk for acute, potentially fatal pancreatitis, in whom response to diet and triglyceride
    lowering therapy has been inadequate. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">WAYLIVRA reduces triglyceride levels by inhibiting the production of apoC-III, a protein that is a key regulator of triglyceride levels.</span>
    WAYLIVRA received conditional marketing authorization in May 2019 from the European Commission, or EC. W<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e sell WAYLIVRA in Europe through our distribution agreement with Sobi.
      In Latin America, WAYLIVRA is approved for two indications, FCS and FPL. PTC is commercializing WAYLIVRA in Brazil and is pursuing access in additional Latin American countries through its exclusive license agreement with us.</span></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAYLIVRA&#8217;s conditional marketing authorization in the EU for FCS and approval in Brazil for FCS we<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">re based </span>on efficacy and safety data from <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the Phase 3 APPROACH study and
      supported by results from the Phase 3 COMPASS study.</span> WAYLIVRA&#8217;s approval in Brazil for FPL was<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> based </span>on efficacy and safety data
    from <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the Phase 3 BROADEN study in patients with FPL.</span></div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Our Innovative Late-Stage Pipeline of Ionis-Owned Investigational Medicines</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As a pioneer in RNA-targeted therapeutics, we continue to drive innovation with a leading pipeline in neurology, cardiology and select
    diseases of high unmet need. The table below lists Ionis-owned medicines currently in late-stage development, which Ionis plans to commercialize in the U.S. independently.</div>

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  <div style="text-align: center;"><img width="702" height="271" src="image01.jpg" alt="graphic" style="height: 271px; width: 702px;"/></div>

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    <td style="width: 18pt; vertical-align: top;"><sup>1</sup></td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis is commercializing TRYNGOLZA (olezarsen) for the treatment of FCS in the U.S.</div>
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    <td style="width: 18pt; vertical-align: top;"><sup>2</sup></td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted Otsuka exclusive rights to commercialize donidalorsen in Europe and Asia-Pacific regions.</div>
        </td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted Theratechnologies exclusive rights to commercialize olezarsen and donidalorsen in Canada.</div>
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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Olezarsen (apoC-III)</span><sub style="font-weight: bold;">&#160;</sub><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8211; </span><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">O</span>lezarsen is an
    investigational RNA-targeted medicine that we are evaluating for people with sHTG. Olezarsen is designed to lower the body&#8217;s production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood. sHTG is a disease
    categorized by triglyceride levels of 500 mg/dL and above. It develops due to primary (genetic) and secondary causes including diet and lifestyle, other medical conditions and certain medications. More than three million people are currently estimated
    to live with sHTG in the U.S. People living with sHTG are at high risk of pancreatitis (a painful inflammation of the pancreas) and damage to the pancreas. As such, reducing the risk of pancreatitis is a critically important reason to treat sHTG.
    People with sHTG are also at risk of heart, brain and blood vessel damage.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are currently conducting a broad development program for olezarsen that includes three fully enrolled Phase 3 studies supporting
    development for the treatment of sHTG: CORE, CORE2 and ESSENCE. Data from the ESSENCE study is expected in mid-2025 and data from the CORE and CORE2 studies are expected in the second half of 2025.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We advanced olezarsen into Phase 3 development based on the
      positive results from a Phase 2 clinical study in patients</span> with hypertriglyceridemia and at high risk of or with established cardiovascular disease, or CVD. In the Phase 2 study, olezarsen achieved statistically significant, dose-dependent
    reductions in fasting triglycerides compared to placebo at all dose levels. Olezarsen also achieved statistical significance in numerous key secondary endpoints, including significant reductions in apoC-III. Olezarsen demonstrated a favorable safety
    and tolerability profile in the Phase 2 study supportive of continued development. As discussed above under &#8220;TRYNGOLZA&#8221; in the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Our
      Marketed Medicines &#8211; Bringing Value to Patients Today</span>, olezarsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> was recently approved in the U.S. for the treatment of FCS.</span></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Donidalorsen (PKK)</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8211; </span>Donidalorsen is an investigational RNA-targeted medicine we designed to target the production of prekallikrein, or PKK, which plays an important role
    in the activation of inflammatory mediators associated with acute attacks of HAE. By reducing the production of PKK, donidalorsen could be an effective prophylactic approach to preventing HAE attacks. HAE is a rare and potentially life-threatening
    genetic condition that involves recurrent attacks of severe swelling (angioedema) in various parts of the body, including the hands, feet, genitals, stomach, face and/or throat. HAE is estimated to affect approximately 20,000 people in the U.S. and
    Europe. Donidalorsen is currently under review in the U.S. and the FDA has set an action date of August 21, 2025 under the Prescription Drug User Fee Act, or PDUFA. Donidalorsen is also under regulatory review in the EU. Otsuka has exclusive rights to
    commercialize donidalorsen in Europe and Asia and Theratechnologies has exclusive rights to commercialize donidalorsen in Canada.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our regulatory submissions are based on the positive data from the placebo-controlled Phase 3 OASIS-HAE study, the Phase 3 OASISplus study
    and the Phase 2 OLE study in patients with HAE. The OASIS-HAE study met its primary endpoint with a statistically significant reduction in the rate of HAE attacks and demonstrated clinically significant improvement in quality of life as measured by the
    Angioedema Quality of Life Questionnaire, or AE-QoL in patients treated every four weeks and patients treated every eight weeks. The OASISplus study includes an OLE cohort and a prospective cohort to assess patients switching from currently available
    long-term prophylactic treatments to donidalorsen. Positive results from a February 2024 data cut from the ongoing OLE cohort showed that HAE attack rates continued to improve over time and extended treatment resulted in further improved quality of
    life measures and high levels of disease control. In the OASISplus switch cohort, patients followed a pre-defined specific protocol to transition from their prior therapy to donidalorsen. Results showed that patients were able to switch to donidalorsen
    from prior prophylactic treatment without an increase in breakthrough attacks. Donidalorsen treatment also led to a further improvement in mean monthly HAE attack rates and continued improvements in measures of quality of life. A majority of patients
    surveyed reported a preference for donidalorsen over their previous treatment. In all of these studies, donidalorsen demonstrated a favorable safety and tolerability profile.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA and EMA granted Orphan Drug designation to donidalorsen.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Zilganersen (GFAP)</span> &#8211; Zilganersen
    (formerly ION373) is an investigational RNA-targeted medicine we designed to inhibit the production of glial fibrillary acidic protein, or GFAP, that accumulates because of disease-causing variants in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">GFAP</span> gene. We are developing zilganersen as a potential treatment for people with genetically confirmed Alexander disease, or AxD. AxD is an ultra-rare, progressive and ultimately fatal
    type of leukodystrophy, which are a group of genetic disorders that affect the brain&#8217;s white matter. AxD is estimated to occur in approximately one in one million to one in three million people worldwide and usually leads to death within 14 - 25 years
    after symptom onset. AxD can present throughout life as loss of independence and lack of ability to control muscles for swallowing, airway protection and purposeful movements. The impact of AxD can vary depending on factors like age of onset.
    Diagnosing AxD is based on a combination of clinical presentation, brain magnetic resonance imaging, or MRI, findings and genetic testing. There are no medicines approved for people with AxD, and current treatments focus on managing their symptoms.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are conducting a single clinical study of zilganersen in patients with AxD designed to assess the efficacy, safety and tolerability
    of zilganersen. In September 2023, we advanced zilganersen into the Phase 3 portion of the study.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">T</span>he FDA and EMA granted Orphan Drug designation to
    zilganersen. Additionally, the FDA granted Fast Track and Rare Pediatric designations to zilganersen.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ION582 (UBE3A)</span> (BIIB121) &#8211; ION582
    is an investigational RNA-targeted medicine we designed to inhibit the expression of the UBE3A antisense transcript, or UBE3A-ATS, and increase production of UBE3A protein, for the potential treatment of AS. AS is a rare, genetic neurological disease
    caused by the loss of function of the maternally inherited <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">UBE3A</span> gene. AS typically presents in infancy and is characterized by intellectual
    disability, balance issues, motor impairment, and debilitating seizures. Some patients are unable to walk or speak. Some symptoms can be managed with existing drugs; however, there are no approved disease modifying therapies.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are conducting the ongoing open label Phase 1/2 study, HALOS, of ION582 in patients with AS designed to assess the safety,
    tolerability and activity of multiple ascending doses of ION582 administered intrathecally. In 2024, we presented positive results from the completed multiple ascending dose, or MAD, portion of the study in people with AS demonstrating consistent and
    encouraging clinical improvement on measures assessing all functional domains including communication, cognition and motor function. ION582 showed favorable safety and tolerability at all dose levels in the study.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on the positive results from the HALOS study and alignment with the FDA, we plan to advance ION582 into Phase 3 development in the
    first half of 2025. The planned placebo-controlled Phase 3 study will enroll children and adults with AS who have a maternal <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">UBE3A</span> gene deletion or
    mutation to assess the efficacy, safety and tolerability of ION582.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA and EMA granted Orphan Drug designation to ION582. Additionally, the FDA granted Fast Track and Rare Pediatric designations to
    ION582.</div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Our Innovative Late-Stage Pipeline of Partnered Investigational Medicines</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our Ionis-owned investigational medicines, we also have numerous potentially transformational partnered medicines in
    clinical development. The table below lists our partnered medicines in late-stage development. For further information on our collaboration agreements, refer to the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>.</div>

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  <div style="text-align: center;"><img width="675" height="270" src="image03.jpg" alt="graphic" style="height: 270px; width: 675px;"/></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Eplontersen (TTR) &#8211; </span>Eplontersen is
    an investigational RNA-targeted medicine designed to degrade mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues. Eplontersen is currently being evaluated
    in patients with hereditary or wild-type transthyretin-mediated amyloid cardiomyopathy, or ATTR-CM. ATTR-CM is a progressive and fatal disease caused by the accumulation of misfolded TTR protein in the cardiac muscle. Patients experience ongoing
    debilitating heart damage resulting in progressive heart failure, which results in death within two to six years from disease onset. Worldwide, there are an estimated 300,000 &#8211; 500,000 patients with ATTR-CM. We and AstraZeneca are co-developing
    eplontersen globally and co-commercializing eplontersen in the U.S. AstraZeneca has exclusive rest-of-world commercialization rights.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are conducting the ongoing placebo-controlled CARDIO-TTRansform Phase 3 cardiovascular outcome study of eplontersen in patients with
    ATTR-CM. We designed the study to evaluate the efficacy, safety and tolerability of eplontersen in patients with ATTR-CM.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed above under &#8220;WAINUA&#8221; in the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Our Marketed Medicines &#8211; Bringing Value to Patients Today</span>, eplontersen is approved in numerous countries, including the U.S. and UK, for the treatment of the ATTRv-PN.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA granted Orphan Drug designation to WAINUA for the treatment of ATTR. The FDA also granted Fast Track designation to eplontersen
    for ATTR-CM.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Pelacarsen (Apo(a)) </span>(TQJ230)<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> &#8211; </span>Pelacarsen is an investigational RNA-targeted medicine we designed to inhibit the production of apolipoprotein(a), or Apo(a), in the liver to offer a
    direct approach for reducing lipoprotein(a), or Lp(a). Elevated Lp(a) is recognized as an independent, genetic cause of CVD. Lp(a) levels are determined at birth and lifestyle modification, including diet and exercise, do not impact Lp(a) levels.
    Inhibiting the production of Apo(a) in the liver reduces the level of Lp(a) in blood, potentially slowing down or reversing CVD in people with hyperlipoproteinemia(a), a condition in which individuals have levels of Lp(a) greater than 50 mg/dL, the
    recognized threshold for risk of CVD. We believe antisense technology is well suited to address hyperlipoproteinemia(a) because it specifically targets the RNA that codes for all forms of the Apo(a) molecule. It is estimated that there are more than
    eight million people living with CVD and elevated levels of Lp(a). <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our partner, Novartis, is responsible for ongoing development and commercialization of pelacarsen
      worldwide.</span></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis is conducting the placebo-controlled Phase 3 cardiovascular outcome study of pelacarsen, Lp(a)HORIZON, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">to assess the efficacy, safety and tolerability of pelacarsen</span> in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">patients with </span>elevated Lp(a) levels and
    established or at risk for CVD.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2018, at the American Heart Association annual meeting, we reported results of the Phase 2 study of pelacarsen in patients
    with hyperlipoproteinemia(a). In the Phase 2 study, we observed statistically significant and dose dependent reductions from baseline in Lp(a) levels. Additionally, pelacarsen demonstrated a favorable safety and tolerability profile in the study.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA and Center for Drug Evaluation of China National Medical Products Administration granted pelacarsen Fast Track designation and
    Breakthrough Therapy, respectively, for the treatment of patients with elevated Lp(a) and established CVD.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Bepirovirsen (HBV) </span>(GSK3228836)<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> &#8211; </span>Bepirovirsen is an investigational RNA-targeted medicine we designed to inhibit the production of viral proteins associated with hepatitis B virus,
    or HBV. These include proteins associated with infection and replication, including the hepatitis B surface antigen, or HBsAg, which is present in both acute and chronic infections and is associated with a poor prognosis in people with chronic HBV
    infection. HBV infection is a serious health problem that can lead to significant and potentially fatal health conditions, including cirrhosis, liver failure and liver cancer. Chronic HBV infection is one of the most common persistent viral infections
    in the world, affecting more than 250 million people and resulting in more than 1 million deaths annually. Currently available therapies, although effective in reducing circulating HBV in the blood, do not effectively inhibit HBV antigen production and
    secretion, which are associated with poor prognosis and increased risk of liver cancer. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our partner, GSK, is responsible for ongoing development and commercialization of
      bepirovirsen worldwide.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">GSK is conducting the placebo-controlled Phase 3 program of bepirovirsen, B-Well, in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">patients with</span> chronic HBV <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">designed to assess the efficacy, safety and tolerability of bepirovirsen</span>.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2022, GSK presented positive results from the Phase 2b B-Clear study of bepirovirsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>in patients with chronic HBV infection. The end of study results showed that treatment with bepirovirsen in some patients resulted in sustained clearance of HBsAg and HBV DNA for 24 weeks
    after end of bepirovirsen treatment in people with chronic HBV infection. Additionally in June 2023, GSK presented durable response data from the Phase 2 B-Sure long-term follow-up study of bepirovirsen in complete responder patients from the Phase 2b
    B-Clear study of patients with HBV. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">And </span>in October 2023, GSK reported positive data from the B-Together Phase 2b study of bepirovirsen in patients with chronic HBV
    infection following sequential treatment with pegylated interferon. Bepirovirsen <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">demonstrated a favorable safety and tolerability profile in these studies.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA and Japanese Ministry of Health, Labour and Welfare, or MHLW, granted bepirovirsen Fast Track designation and SENKU (formerly
    known as SAKIGAKE) designation, respectively, for the treatment of patients with chronic HBV infection.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Sefaxersen (IgAN) </span>(<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">RO7434656)</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> &#8211;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Sefaxersen (formerly IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">) is an investigational </span>RNA-targeted<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> medicine we designed to reduce the production of complement factor B, or FB, and to lower activation of the alternative complement pathway. Genetic association studies have shown that overaction of the alternative complement
      pathway has been associated with the development of several complement-mediated diseases, including immunoglobulin A nephropathy, or IgAN. IgAN is one of the most common causes of inflammation that impairs the filtering ability of kidneys and is an
      important cause of chronic kidney disease and kidney failure. Also known as Berger&#8217;s disease, IgAN is characterized by deposits of IgA in the kidneys, resulting in inflammation and tissue damage. Our partner, Roche, is responsible for ongoing
      development and commercialization of sefaxersen worldwide.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2023, Roche initiated a placebo-controlled Phase 3 study of sefaxersen, called IMAGINATION, in patients with IgAN designed to
    assess the efficacy, safety and tolerability of sefaxersen.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reported positive results from a Phase 2 open-label study of sefaxersen in patients with IgAN, demonstrating robust and sustained
    reductions in complement FB and other key measures of the alternative complement pathway. Sefaxersen treatment also resulted in sustained reductions in proteinuria with patients maintaining kidney function, as measured by estimated glomerular
    filtration rate, or eGFR, during six months of treatment. Sefaxersen demonstrated a favorable safety and tolerability profile in the study.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Ulefnersen (FUS)</span> &#8211; Ulefnersen is
    an investigational RNA-targeted medicine we designed to reduce the production of the fused in sarcoma, or FUS, protein to treat people with Amyotrophic lateral sclerosis, or ALS, caused by mutations in the FUS gene. Because antisense-mediated reduction
    of mutant FUS protein in a FUS-ALS mouse model demonstrated the ability to prevent motor neuron loss, it is hypothesized that reduction of FUS protein will reverse or prevent disease progression in FUS-ALS patients. FUS-ALS is a rare, fatal,
    neurodegenerative disorder characterized by muscle weakness, loss of movement, and difficulty breathing and swallowing, resulting in a severely declining quality of life and eventually death. Current treatment options are extremely limited, with no
    medicines that significantly slow disease progression. Our partner, Otsuka, is responsible for global regulatory and commercialization activities, and costs for ulefnersen.</div>

  <div style="text-align: justify; text-indent: 35.3pt;"><br/>
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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we initiated a Phase 3 study of ulefnersen in patients with FUS-ALS designed to assess the efficacy, safety and
    tolerability of ulefnersen.</div>

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  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA and EMA granted Orphan Drug designation to ulefnersen.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Our Innovative Mid-Stage Pipeline of Investigational Medicines</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have a rich mid-stage pipeline with numerous potentially transformational investigational medicines, including both Ionis-owned
    and partnered therapies. The table below lists our medicines in mid-stage development. For further information on our collaboration agreements, refer to the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>.</div>

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  <div style="text-align: center;"><img width="690" height="422" src="image04.jpg" alt="graphic" style="height: 422px; width: 690px;"/></div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our Technology</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For three decades through our innovations in science and technology, we have enhanced the profiles of RNA-targeted medicines in addition
    to advancing new approaches in genetic medicine.<span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#160;</span>Our recent technology advancements have enabled us to advance programs with the potential for
    extended dosing and delivery to new tissues, such as muscle. We have also added capabilities to utilize small interfering RNA, or siRNA, and potentially gene editing in addition to our novel antisense technology, which gives us the potential to deliver
    medicines to a greater number of people living with serious diseases.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Overview of Ionis&#8217; Technology</div>

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  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All of the medicines currently in our clinical pipeline use our antisense technology &#8212; an innovative platform for discovering
    first-in-class and/or best-in-class medicines. Antisense medicines target RNA, the intermediary that conveys genetic information from a gene to the protein synthesis machinery in the cell. By targeting RNA instead of proteins, we can use antisense
    technology to increase, decrease or alter the production of specific proteins. Most of our antisense medicines are designed to bind to mRNAs and inhibit the production of disease-causing proteins. Examples of these include WAINUA, TRYNGOLZA and
    donidalorsen. SPINRAZA is an example of an antisense medicine that modulates RNA splicing to increase protein production of the SMN protein, which is critical to the health and survival of nerve cells in the spinal cord that are responsible for
    neuro-muscular function. The SMN protein is deficient in people with SMA. Our antisense technology is also broadly applicable additional antisense mechanisms including decreasing toxic RNAs.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also now use siRNA technology, in addition to antisense technology to develop new medicines. Like antisense, siRNA medicines target
    RNA, and can decrease the production of specific proteins involved in disease. For each program we work on, we choose the approach that demonstrates the best potential product profile for the indication we are pursuing.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our advanced LIgand-Conjugated Antisense, or LICA, technology is a chemical technology we developed that involves attaching a molecule
    called a ligand that binds with receptors on the surface of cells in a highly specific manner. Because these receptors are often found only on certain cell types, LICA allows us to increase effective delivery of our antisense medicines with higher
    specificity to certain cell types that express these receptors relative to non-conjugated antisense medicines. We currently have an integrated assessment of data from multiple LICA medicines and clinical programs that demonstrates that our LICA
    technology for liver targets can increase potency by 20-30-fold over our non-LICA antisense medicines. Our LICA medicines have also demonstrated consistently favorable safety and tolerability in clinical trials, including in our Phase 3 studies of
    WAINUA (for ATTRv-PN), TRYNGOLZA (for FCS patients) and donidalorsen (for HAE).</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Emerging Technology Advancements</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our recent technology advancements have enabled us </span>to







    create even more potent medicines amenable to new potential targets and tissue types. We have also diversified the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">approaches we can use in designing our medicines to reach
      more patients with severe diseases.</span> Today our medicines and those entering our pipeline utilize our key technology advances, including Bicycle technology, siRNA technology and MsPA backbone chemistry. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">And through our Metagenomi collaboration, we added the potential to use gene editing, which modifies DNA.</span></div>

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  <div style="text-align: justify; margin-left: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Mesyl phosphoramidate Backbone Chemistry</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We designed our MsPA backbone chemistry to improve both therapeutic index and durability. It does this by increasing metabolic stability
    relative to the other backbone chemistries we utilize. We have also shown it can improve potency in certain circumstances and reduce non-specific interactions with proteins that can cause undesirable effects, such as proinflammatory effects. We
    currently have multiple new programs using our MsPA backbone in preclinical development.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bicycle Collaboration</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we entered into a collaboration with Bicycle Therapeutics that we expect can expand our LICA platform to target both skeletal
    and cardiac muscle, and potentially deliver medicines across the blood brain barrier. Bicycles are small, bicyclic peptides that have high affinity and selectivity for protein targets. Our collaboration with Bicycle allows us to utilize Bicycles that
    bind transferrin receptor 1 to facilitate the tissue specific delivery of oligonucleotide drugs (both antisense and siRNAs). We advanced our first program that utilizes Bicycle technology into preclinical development in 2023.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Gene Editing and Metagenomi Collaboration</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, we entered into a collaboration with Metagenomi that leverages our extensive expertise in RNA-targeted therapeutics and
    Metagenomi&#8217;s next-generation gene editing systems to pursue a mix of validated and novel genetic targets with the goal of discovering and developing new drugs. These targets have the potential to expand therapeutic options for patients.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gene editing utilizes specific RNA-guided nucleases known as Cas enzymes to precisely and permanently modify a DNA sequence. Because of
    this, gene editing holds the promise of treatments that could provide long-term, potentially permanent, therapeutic benefits.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gene editing is highly complementary and synergistic with RNA-targeted therapeutics. Both platforms rely on the same nucleic acid
    hybridization principals to precisely target nucleases to either RNA, in the case of RNase H and siRNA drugs, or to DNA in the case of Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR-Cas systems. This enables us to leverage our
    expertise in nucleic acids and modified nucleic acid chemistry with the goal to enhance gene editing&#8217;s ability to treat diseases for which there are limited treatment options.</div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Collaborative Arrangements</div>

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  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have established alliances with a number of leading global pharmaceutical companies. Our partners include the following companies,
      among others: AstraZeneca, Biogen, GSK, Novartis, Otsuka and Roche. Through our partnerships, we have earned both commercial revenue and a broad and sustaining base of R&amp;D revenue in the form of license fees, upfront payments and milestone
      payments. We are also eligible to receive royalties and additional milestones under our partnerships. Below, we include the significant terms of our collaboration agreements. For additional details, including other financial information, refer to
      Part IV, Item 15, Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements,</span> in the Notes to the Consolidated Financial Statements.</div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">AstraZeneca</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">WAINUA (Eplontersen) Collaboration</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for
    the treatment of ATTR. The FDA and Health Canada approved eplontersen with the brand name, WAINUA, for ATTRv-PN, while the Medicines and Healthcare products Regulatory Agency, or MHRA, approved WAINUA for ATTRv-PN in the UK as WAINZUA. Under the
    agreement, we are jointly developing WAINUA with AstraZeneca worldwide for ATTRv-PN and ATTR cardiomyopathy, or ATTR-CM. We are jointly commercializing WAINUA with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize WAINUA
    outside the U.S.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The collaboration includes territory-specific development, commercial and medical affairs cost-sharing provisions. AstraZeneca is
    currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. AstraZeneca is responsible for the vast majority of the commercial and medical affairs costs in the U.S. and all costs associated with
    bringing WAINUA to market outside the U.S.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive an upfront payment, development and approval milestone payments and sales
    milestone payments. In addition, we are eligible to receive up to mid-20 percent royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.S.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. As a result, we began earning
    royalties from WAINUA sales, which we recognize as commercial revenue in our consolidated statements of operations.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From inception through December 31, 2024,
    we have generated more than $520 million in payments under this collaboration, including milestone payments for the approval of WAINUA in the U.S. and UK, revenue we earned from cost sharing provisions and royalties.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Cardiovascular, Renal and Metabolic Collaboration</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have a collaboration with AstraZeneca focused on discovering and developing treatments for cardiovascular, renal and metabolic
    diseases, which we formed in 2015. Under our collaboration, AstraZeneca has licensed multiple medicines from us. AstraZeneca is responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has
    licensed from us.</div>

  <div><br/>
  </div>

  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive an upfront payment, license fees, development milestone payments,
      regulatory milestone payments and sales milestone payments. In addition, we are eligible to receive tiered royalties up to 10 percent on net sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. From
      inception through December 31, 2024, we have generated more than $370 million in payments under this collaboration.</div>

  </div>

  <div>
    <div><br/>
    </div>

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    </div>

  </div>

  <div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Biogen</div>

  </div>

  <div>
    <div><br/>
    </div>

  </div>

  <div>
    <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Marketed Medicines</div>

    <div><br/>
    </div>

    <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>

    <div><br/>
    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2012, we entered into a collaboration agreement with
      Biogen to develop and commercialize SPINRAZA.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are receiving tiered royalties ranging from 11 percent to 15 percent on sales of SPINRAZA. Under our agreement,
      Biogen is responsible for global development, regulatory and commercialization activities and costs for SPINRAZA. From inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recognized more than $2.3 billion in total revenue under this collaboration, including approximately $1.9 billion in revenue from SPINRAZA
      royalties and more than $425 million in R&amp;D revenue.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have exclusively in-licensed patents related to SPINRAZA from Cold Spring Harbor Laboratory and the University of Massachusetts. We pay
    Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on net sales of SPINRAZA.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">QALSODY</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2018, Biogen exercised its option to license QALSODY from us. We are receiving tiered royalties ranging from 11 percent to 15 percent
    on net sales of QALSODY. Under our agreement, Biogen is responsible for global development, regulatory and commercialization activities and costs for QALSODY. Biogen is also evaluating QALSODY as a potential treatment for presymptomatic SOD1-ALS
    patients in the ongoing ATLAS study. From inception through December 31, 2024, we recognized more than $110 million in total revenue under this collaboration, including approximately $4 million in revenue from QALSODY royalties and $108 million in
    R&amp;D revenue.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">New antisense medicines for the treatment of SMA</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2017, we entered into a collaboration agreement with Biogen to identify new antisense medicines for the treatment of SMA. In 2021,
    Biogen exercised its option to license ION306. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen is solely responsible for the costs and expenses related to the development, manufacturing and potential future
      commercialization of ION306 following the option exercise. </span>We will receive development and regulatory milestone payments from Biogen if new medicines, including ION306, advance towards marketing approval.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of this collaboration, we are eligible to receive development, regulatory and sales milestone payments. In addition, we are
    eligible to receive tiered royalties from the mid-teens to mid-20 percent range on net sales from any product that Biogen successfully commercializes under this collaboration. From inception through December 31, 2024, we have generated $85 million in payments under this collaboration.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Neurology Collaborations</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have multiple collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders,
    including our 2018 and 2012 neurology collaborations. Under these collaborations, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for certain neurological diseases and the option to license certain medicines
    resulting from these collaborations. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For each medicine under these collaborations, we are eligible to receive a license fee, development milestone payments and regulatory
    milestone payments. In addition, we are eligible to receive tiered royalties up to the 20 percent range on net sales from any products that Biogen successfully commercializes under these collaborations. We are currently advancing multiple programs
    under this collaboration. From inception through December 31, 2024, we have generated more than $1.3 billion in payments under these
    collaborations.</div>

  <div><br/>
  </div>

  <div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">GSK</div>

  </div>

  <div>
    <div><br/>
    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2010, we entered into a collaboration with GSK using our antisense drug discovery platform to discover and develop new medicines
    against targets for serious and rare diseases, including infectious diseases. Under our collaboration, GSK is developing bepirovirsen for the treatment of chronic HBV infection. In 2019, following positive Phase 2 results, GSK licensed our HBV program.
    GSK is responsible for all global development, regulatory and commercialization activities and costs for the HBV program.</div>

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    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive an upfront payment, a license fee, development milestone payments,
    regulatory milestone payments and sales milestone payments if GSK successfully develops and commercializes bepirovirsen. In addition, we are eligible to receive tiered royalties up to the low-teens on net sales of bepirovirsen. From inception through December 31, 2024, we have generated more than $105 million in payments under the HBV program collaboration.</div>

  <div>
    <div><br/>
    </div>

  </div>

  <div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Novartis</div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Pelacarsen Collaboration</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2017, we initiated a collaboration with Novartis to develop and commercialize pelacarsen for patients with elevated Lp(a) and CVD.
    Novartis is responsible for conducting and funding development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study that Novartis initiated in 2019.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Over the term of the collaboration, we are eligible to
      receive an upfront payment, a license fee, a development milestone payment, regulatory milestone payments and sales milestone payments. We are also eligible to receive tiered royalties in the mid-teens to low 20 percent range on net sales of
      pelacarsen</span>. From inception through December 31, 2024, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e
      have generated more than $275 million in payments under this collaboration.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">New Medicine for the Treatment of Lp(a)-Driven Cardiovascular Disease</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2023, we entered into a collaboration and license agreement with Novartis for the discovery, development and commercialization of a
    novel medicine for patients with Lp(a)-driven cardiovascular disease, or CVD. Novartis is solely responsible for the development, manufacturing and potential commercialization of the next generation Lp(a) medicine.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive an upfront payment, development milestone payments, regulatory milestone
    payments and sales milestone payments. In addition, we are eligible to receive tiered royalties ranging from 10 percent to 20 percent on net sales. From inception through December 31, 2024, we have generated more than $65 million in payments under this collaboration.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Roche</div>

  <div>
    <div><br/>
    </div>

  </div>

  <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Sefaxersen for Complement-Mediated Diseases</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2018, we entered into an agreement with Roche to develop sefaxersen for the treatment of complement-mediated diseases, including IgAN,
    and geographic atrophy, or GA. In April 2023, Roche initiated a Phase 3 study of sefaxersen in patients with IgAN.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After positive data from a Phase 2 clinical study in patients with IgAN, Roche licensed sefaxersen in 2022. As a result, Roche is
    responsible for global development, regulatory and commercialization activities, and costs for sefaxersen.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2024, Roche discontinued development of sefaxersen for the treatment of GA, the advanced stage of dry age-related macular
    degeneration, following the completion of the Phase 2 study, which showed a favorable safety profile and target engagement, but insufficient efficacy to advance into Phase 3 development.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive a license fee, development milestone payments, regulatory milestone
    payments and sales milestone payments. We are also eligible to receive tiered royalties from the high teens to 20 percent on net sales. From inception through December 31, 2024, we have generated more than $140 million in payments under this collaboration.</div>

  <div><br/>
  </div>

  <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Huntington&#8217;s Disease</div>

  <div>
    <div><br/>
    </div>

  </div>

  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2013, we entered into an agreement with Hoffmann-La Roche Inc. and F. Hoffmann-La Roche Ltd, collectively Roche, to develop
      treatments for Huntington&#8217;s disease, or HD, based on our antisense technology. Under the agreement, we discovered and developed tominersen, an investigational antisense medicine targeting HTT protein. We developed tominersen through completion of our
      Phase 1/2 clinical study in people with early-stage HD. In 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. As a result, Roche is responsible for all global development, regulatory and commercialization
      activities and costs for tominersen.</div>

    <div><br/>
    </div>

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    </div>

  </div>

  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive a license fee, development milestone payments, regulatory milestone
      payments and sales milestone payments as tominersen advances. In addition, we are eligible to receive milestone payments for each additional medicine successfully developed. We are also eligible to receive tiered royalties up to the mid-teens on net
      sales of any product resulting from this collaboration. From inception through December 31, 2024, we have generated more than $150 million&#160;
      in payments under this collaboration.</div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RNA-Targeting Medicines for Alzheimer&#8217;s Disease and Huntington&#8217;s Disease</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2023, we entered into an agreement with Roche to develop two undisclosed early-stage programs for RNA-targeting
    investigational medicines for the treatment of Alzheimer&#8217;s disease, or AD, and HD. Under the agreement, we are responsible for advancing the two programs through preclinical studies and Roche is responsible for clinical development, manufacturing and
    commercialization of the medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive an upfront payment, development milestone payments and sales milestone
    payments. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales. From inception through December 31, 2024,
    we have generated more than $60 million in payments under this collaboration.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Commercialization Partnerships</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Otsuka</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2023, we entered into an agreement with Otsuka Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe.
    In the second quarter of 2024, we expanded the agreement to include commercialization rights for donidalorsen in the Asia-Pacific region. We are responsible for the ongoing development of donidalorsen.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2024, we entered into an agreement with Otsuka to commercialize ulefnersen worldwide. We are responsible for the ongoing
    development of ulefnersen.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaborations, we are eligible to receive upfront payments, regulatory milestone payments and sales milestone
    payments. In addition, we are eligible to receive tiered royalties up to 30 percent on net sales. From inception through December 31, 2024, we
    have generated more than $110 million in payments under these collaborations.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PTC Therapeutics</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, we entered into an exclusive license agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin
    America and certain Caribbean countries. Under the license agreement, we are eligible to receive royalties from PTC in the mid-20 percent range on net sales for each medicine. In December 2021 and September 2023, we started receiving royalties from PTC
    for TEGSEDI and WAYLIVRA sales, respectively. From inception through December 31, 2024, we have generated more than $55 million in payments
    under this collaboration.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Swedish Orphan Biovitrum AB (Sobi)</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We began commercializing TEGSEDI and WAYLIVRA in Europe in January 2021 and TEGSEDI in North America in April 2021 through distribution
    agreements with Sobi. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. In exchange, we earn a distribution fee on net sales from Sobi for each
    medicine. In October 2023, our agreement for TEGSEDI in North America was terminated and we discontinued TEGSEDI in North America in 2024. From inception through December 31, 2024, we have generated more than $60 million in payments under this collaboration.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Theratechnologies</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2024, we entered into an agreement with Theratechnologies, Inc. to commercialize donidalorsen and olezarsen in Canada. We are
    responsible for the ongoing development of donidalorsen and olezarsen.</div>

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    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Technology Enhancement Collaborations</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bicycle Therapeutics</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2020, we entered into a collaboration agreement with Bicycle Therapeutics, or Bicycle, and obtained an option to license its peptide
    technology that we expect can expand our LICA platform to target both skeletal and cardiac muscle, and potentially deliver medicines across the blood brain barrier. In 2021, we exercised our option to license Bicycle&#8217;s technology. Our payment to
    Bicycle for licensing its technology included an equity investment in Bicycle. In addition, we will pay Bicycle milestone payments and royalties that are contingent on the achievement of certain development, regulatory and sales events.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Metagenomi</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, we entered into a collaboration and license agreement with Metagenomi to research, develop and commercialize investigational
    medicines for up to four initial genetic targets, and, upon the achievement of certain development milestones, four additional genetic targets using gene editing technologies. As a result, we paid Metagenomi to license its technologies and will pay
    Metagenomi certain fees for the selection of genetic targets. In addition, we will pay Metagenomi milestone payments and royalties that are contingent on the achievement of certain development, regulatory and sales events. We will also reimburse
    Metagenomi for certain of its costs in conducting its research and drug discovery activities under the collaboration.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Vect-Horus</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2023, we entered into a license agreement with Vect-Horus to provide us with a worldwide, exclusive license for a specified
    number of targets using Vect-Horus&#8217; platform technology &#8220;VECTrans&#8221; for systemic delivery of RNA-targeted therapeutics that may cross the blood-brain barrier and address targets in the central nervous system. We will pay Vect-Horus milestone payments
    and royalties that are contingent on the achievement of certain development, regulatory and sales events.</div>

  <div>
    <div><br/>
    </div>

    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Other Agreements</div>

  </div>

  <div>
    <div><br/>
    </div>

    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Alnylam Pharmaceuticals, Inc.</div>

    <div><br/>
    </div>

    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of our agreement with Alnylam, we co-exclusively (with ourselves) licensed to Alnylam our patent estate relating to
      antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics, with Alnylam having the exclusive right to grant platform sublicenses for double-stranded RNAi. In exchange for such rights, we are eligible to earn
      a technology access fee, participate in fees from Alnylam&#8217;s partnering programs and earn future milestone and royalty payments from Alnylam. We retained exclusive rights to our patents for single-stranded antisense therapeutics and for a limited
      number of double-stranded RNAi therapeutic targets and all rights to single-stranded RNAi, or ssRNAi, therapeutics. In turn, Alnylam nonexclusively licensed to us its patent estate relating to antisense motifs and mechanisms and oligonucleotide
      chemistry to research, develop and commercialize single-stranded antisense therapeutics, ssRNAi therapeutics, and to research double-stranded RNAi compounds. We also received a license to develop and commercialize double-stranded RNAi therapeutics
      targeting a limited number of therapeutic targets on a nonexclusive basis. Additionally, in 2015, we and Alnylam entered into an alliance in which we cross-licensed intellectual property. Under this alliance, we and Alnylam each obtained exclusive
      license rights to four therapeutic programs. Alnylam granted us an exclusive, royalty-bearing license to its chemistry, RNA targeting mechanism and target-specific intellectual property for oligonucleotides against four targets, including FXI and
      Apo(a) and two other targets. In exchange, we granted Alnylam an exclusive, royalty-bearing license to our chemistry, RNA targeting mechanism and target-specific intellectual property for oligonucleotides against four other targets. Alnylam also
      granted us a royalty-bearing, non-exclusive license to new platform technology arising from May 2014 through April 2019 for single-stranded antisense therapeutics. In turn, we granted Alnylam a royalty-bearing, non-exclusive license to new platform
      technology arising from May 2014 through April 2019 for double-stranded RNAi therapeutics.</div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Manufacturing</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We manufacture most of the active pharmaceutical ingredients, or APIs, we use for our research and development, or R&amp;D, activities
    ourselves. We have also manufactured API and commercial supply for our approved medicines. We have dedicated significant resources to develop ways to improve manufacturing efficiency and capacity. Since we can use variants of the same nucleotide
    building blocks and the same type of equipment to produce our oligonucleotide medicines, we found that the same techniques we used to efficiently manufacture one oligonucleotide medicine could help improve the manufacturing processes for our other
    medicines. By developing several proprietary chemical processes to scale up our manufacturing capabilities, we have greatly reduced the cost of producing oligonucleotide medicines. For example, we have significantly reduced the cost of raw materials
    through improved yield efficiency, while at the same time increasing our capacity to make our medicines. Through both our internal research and development programs and collaborations with outside vendors, we may achieve even greater efficiency and
    further cost reductions.</div>

  <div><br/>
  </div>

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    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our manufacturing facility is located in a 26,800 square foot building in Carlsbad, California. We purchased this building in 2017. In
    addition, we have a 25,800 square foot building that houses support functions for our manufacturing activities. We lease this facility under a lease that has a term ending in August 2026 with an option to extend the lease for an additional five-year
    period. Our manufacturing facility is subject to periodic inspections by the FDA and foreign equivalents to ensure that it is operating in compliance with current Good Manufacturing Practices, or cGMP, requirements.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As part of our collaborations, we may agree to manufacture clinical trial material and/or commercial drug supply for our partners. For
    example, in the past we have manufactured clinical trial material for AstraZeneca, Biogen, GSK, Roche, and Novartis and commercial drug supply for Biogen.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe we have sufficient manufacturing capacity at our own facility or at contract manufacturing organizations, or CMOs, to meet our
    current internal research, development and potential commercial needs, as well as our obligations under existing agreements with our partners for research, development and commercial material. We and/or our CMOs manufacture process performance
    qualification batches and pre-approval inspection batches of our Phase 3 medicines that may be used for regulatory submissions and, pending regulatory approval, commercial sale. We believe our current network of CMOs are capable of providing sufficient
    quantities to meet anticipated commercial demands. Additionally, we continue to evaluate relationships with additional suppliers to increase overall capacity and diversify our supply chain. We plan to leverage our relationships with CMOs to maintain
    long-term supply at competitive prices in the future. While we believe that there are alternate sources of supply that can satisfy our commercial requirements, it is possible that identifying and establishing relationships with such sources, if
    necessary, could result in significant delay or material additional costs. We also could experience a disruption in supply from our current CMOs.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CMOs are subject to the FDA&#8217;s cGMP requirements and other rules and regulations prescribed by foreign regulatory authorities. We depend on
    our CMOs for continued compliance with cGMP requirements and applicable foreign standards.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Specifically, we have the following in place for our commercial medicines and our late-stage medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">TRYNGOLZA/Olezarsen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For TRYNGOLZA&#8217;s commercial drug supply, we are using CMOs to produce API and finished goods.&#160; For the ongoing olezarsen clinical studies,
    we and/or our CMOs have supplied the API and the finished drug product. We intend to leverage our relationships with CMOs to meet and maintain long-term commercial supply at competitive prices in the future. We plan to accomplish this through a
    combination of maintaining adequate levels of safety stock and increasing the batch sizes to support future indications.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">WAINUA/Eplontersen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AstraZeneca is responsible for WAINUA&#8217;s commercial drug supply. Our CMOs supplied the API and the finished drug product for WAINUA&#8217;s Phase
    3 program. Pursuant to our collaboration with AstraZeneca, we will supply WAINUA using CMOs for the ongoing clinical trials.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen is responsible for SPINRAZA drug supply.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">QALSODY</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen is responsible for QALSODY drug supply.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">TEGSEDI and WAYLIVRA</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For TEGSEDI&#8217;s commercial drug supply, we are using CMOs to produce API and finished goods for ourselves, Sobi and PTC. For WAYLIVRA&#8217;s
    commercial drug supply, we are using API that we have manufactured and CMOs to produce the finished goods.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Donidalorsen, Zilganersen, Ulefnersen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We and/or our CMOs have supplied the API and the finished
      drug product for </span>donidalorsen, zilganersen and ulefnersen that we believe will be <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">sufficient through the completion of the Phase 3 programs for each medicine,
      including process performance qualification batches.</span></div>

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    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">ION582</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We supplied API and drug product for the ION582 Phase 1 and Phase 2 programs and will continue to supply drug for further clinical
    programs.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Pelacarsen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We supplied API and finished drug product for pelacarsen&#8217;s Phase 3 program. Pursuant to our collaboration with Novartis, Novartis is
    responsible for any further pelacarsen drug supply.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bepirovirsen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We supplied API for bepirovirsen&#8217;s Phase 1 and Phase 2 programs. Pursuant to our collaboration with GSK, GSK is responsible for any
    further bepirovirsen drug supply.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Sefaxersen (IONIS-FB-L<sub>Rx</sub>)</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We supplied API for the sefaxersen Phase 1 and Phase 2 IgAN programs. Pursuant to our collaboration with Roche, Roche is responsible for
    any further drug supply for sefaxersen.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Commercial Operations</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have established sales and marketing capabilities to support our commercial launch of WAINUA and TRYNGOLZA in the U.S. and anticipated
    near-term commercial launch of donidalorsen. We began with our co-commercialization partnership with AstraZeneca for WAINUA in which we combine our experience in RNA-targeted therapeutics and deep knowledge of the TTR amyloidosis market with
    AstraZeneca&#8217;s global scale in drug development and commercialization to enable market penetration for the benefit of patients.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">With our first independent commercial launch of TRYNGOLZA underway, we have entered a new chapter as a fully integrated commercial-stage
    biotechnology company. We have been refining our portfolio strategy and recruiting experienced professionals with relevant backgrounds in sales, marketing, patient education, market access, portfolio planning and market insight, new product commercial
    strategy and commercial operations in the pharmaceutical industry. We are focused on developing a unique and innovative approach to bring our medicines to patients living with serious diseases. We have built core capabilities and a commercial platform
    with the ability to scale as needed to meet our current and future commercialization needs. In addition, we established our TRYNGOLZA field sales team during 2024 and plan to build additional field teams as we approach each of our launches.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medical Affairs</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have built medical affairs capabilities to disseminate information about our medicines and increase disease awareness through various
    channels of communication with key stakeholders. Our medical affairs function is responsible for funding and coordinating investigator-sponsored trials, communicating scientific and clinical information to healthcare providers, medical professionals
    and patients, and managing publications.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intellectual Proprietary Rights</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We rely on patents, trademarks, trade secrets, and proprietary know-how to develop and maintain a competitive position in RNA-targeted
    therapeutics generally and to protect our investment in specific products. To this end, we focus our resources on intellectual property, or IP, that drives value for our company.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Product-Specific IP</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Each of our medicines is protected worldwide by product-specific patents claiming oligonucleotides having the nucleobase sequences and
    chemical modifications of our medicines; and methods of achieving cellular or clinical endpoints using such oligonucleotides. We pursue such patents in significant markets and/or countries for each medicine in development. We also seek to maximize
    patent term. In some cases, the patent term can be extended to recapture a portion of the term lost during regulatory review. Expiration dates listed below do not reflect any such extensions.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial products are also protected by trademarks filed throughout the world.</div>

  <div><br/>
  </div>

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    </div>

  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Marketed Products</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">TRYNGOLZA/Olezarsen and ApoC-III</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe TRYNGOLZA (olezarsen) is protected from generic competition in the U.S. and Europe until at least 2034. Additional patent
    applications to protect olezarsen in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting olezarsen in the U.S. and Europe.</div>

  <div><br/>
  </div>

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<table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">United States</span></div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,163,239</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN C-III EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of olezarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,593,333</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION IN LIPOPROTEIN LIPASE DEFICIENT (LPLD) POPULATIONS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating lipoprotein lipase deficiency with an apo-CIII specific inhibitor wherein triglyceride levels are reduced</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,157,082</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN CIII (APOCIII) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of using apo-CIII antisense compounds for reducing pancreatitis and chylomicronemia and increasing HDL</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2991656</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN C-III EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of olezarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2956176</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION IN LIPOPROTEIN LIPASE DEFICIENT (LPLD) POPULATIONS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating lipoprotein lipase deficiency with an apo-CIII specific inhibitor wherein triglyceride levels are reduced</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3357497</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN CIII (APOCIII) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of using apo-CIII antisense compounds for reducing pancreatitis and chylomicronemia and increasing HDL</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4119569</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CONJUGATED ANTISENSE COMPOUNDS FOR USE IN THERAPY</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2036</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of administering olezarsen at identified doses</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Trademark</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The name &#8220;TRYNGOLZA&#8221; is protected by trademarks throughout the world.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">WAINUA/WAINZUA/Eplontersen <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">and Transthyretin</span></div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Patents</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe WAINUA/WAINZUA (eplontersen) is protected from generic competition in the U.S. and Europe until at least 2034. Additional
    patent applications to protect WAINUA/WAINZUA in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting WAINUA/WAINZUA in the U.S. and Europe:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">United States</span></div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,683,499</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING TTR EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of eplontersen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3524680</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING TTR EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of eplontersen</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Trademarks</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The names &#8220;WAINUA&#8221; and &#8220;WAINZUA&#8221; are protected by trademarks owned by our commercial partner Astra Zeneca.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">SPINRAZA and Survival Motor Neuron 2</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Patents</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe SPINRAZA (nusinersen) is protected from generic competition in the U.S. until at least 2035 and in Europe until at least 2030
    by a suite of patents. These issued patents include: (i) patents licensed from the University of Massachusetts drawn to antisense compounds having the sequence of SPINRAZA, independent of chemical modification, and uses of such compounds for treating
    SMA, (ii) joint patents with Cold Spring Harbor Laboratory claiming fully modified 2&#8217;-MOE compounds targeting SMN2, including the precise composition of matter of SPINRAZA and methods of using such compositions; and (iii) dosing and therapeutic methods
    of using such compounds and compositions. With Biogen&#8217;s license of SPINRAZA, we assigned our interest in these patents to Biogen. The table below lists some key issued patents protecting SPINRAZA in the U.S. and Europe:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,266,822</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of increasing exon-7 containing SMN2 mRNA in a cell using an oligonucleotide having the sequence of SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,110,560</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of using antisense oligonucleotides having sequence of SPINRAZA to alter splicing of SMN2 and/or to treat SMA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1910395</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sequence and chemistry (full 2&#8217;-MOE) of SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3308788</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pharmaceutical compositions that include SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,838,657</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides having sequence of SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,361,977</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sequence and chemistry (full 2&#8217;-MOE) of SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,980,853</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of administering SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,717,750</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of administering SPINRAZA to a patient</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3449926</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pharmaceutical compositions that include SPINRAZA for treating SMA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3305302</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense compounds including SPINRAZA for treating SMA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,926,559</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA doses for treating SMA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,436,802</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS FOR TREATING SPINAL MUSCULAR ATROPHY</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA dosing regimen for treating SMA</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Trademarks</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The name &#8220;SPINRAZA&#8221; is protected throughout the world by trademarks owned by our commercial partner Biogen.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">QALSODY and SOD-1</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Patents</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe QALSODY is protected from generic competition in the U.S. and Europe until at least 2035. Additional patent applications
    designed to protect QALSODY in other foreign jurisdictions are being pursued. With Biogen&#8217;s license of QALSODY, we assigned our interest in these patents to Biogen. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The table
      below lists some key issued patents protecting QALSODY</span> in the U.S. and Europe:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,385,341</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of QALSODY</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,669,546</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating a SOD-1 associated neurodegenerative disorder by administering QALSODY</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,968,453</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating a SOD-1 associated neurodegenerative disorder by administering a pharmaceutical composition of QALSODY</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3126499</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Composition of </span>QALSODY</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Trademarks</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The name &#8220;QALSODY&#8221; is protected throughout the world by trademarks owned by our commercial partner Biogen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">TEGSEDI and Transthyretin</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Patents</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe TEGSEDI (inotersen) is protected from generic competition in the U.S. and Europe until at least 2031. The table below lists
    some key issued patents protecting TEGSEDI<sub>&#160;</sub>in the U.S. and Europe:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,101,743</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense sequence and chemistry of TEGSEDI</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,697,860</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">DIAGNOSIS AND TREATMENT OF DISEASE</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of TEGSEDI</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,061,044</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sodium salt composition of TEGSEDI</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,399,774</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating transthyretin amyloidosis by administering TEGSEDI</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2563920</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of TEGSEDI</div>
        </td>

  </tr>


</table>
  <div style="text-align: left; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Trademarks</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The name &#8220;TEGSEDI&#8221; is protected by trademark throughout the world.</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">WAYLIVRA and ApoC-III</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Patents</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe WAYLIVRA (volanesorsen) is protected from generic competition in Europe until at least 2034. We have obtained patent claims in
    the U.S. and Europe drawn to the use of antisense compounds complementary to a broad active region of human ApoC-III, including the site targeted by WAYLIVRA. We have also obtained issued patents claiming the specific sequence and chemical composition
    of WAYLIVRA in the U.S. and Europe. The table below lists some key issued patents protecting WAYLIVRA in the U.S. and Europe:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,157,082</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of using apo-CIII antisense compounds for reducing pancreatitis and chylomicronemia and increasing HDL</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,593,333</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION IN LIPOPROTEIN LIPASE DEFICIENT (LPLD) POPULATIONS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating lipoprotein lipase deficiency with an apo-CIII specific inhibitor wherein triglyceride levels are reduced</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2956176</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION IN LIPOPROTEIN LIPASE DEFICIENT (LPLD) POPULATIONS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Apo-CIII specific inhibitors including WAYLIVRA for treating lipoprotein lipase deficiency or FCS</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Trademark</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The name &#8220;WAYLIVRA&#8221; is protected by trademark in Europe.</div>

  <div><br/>
  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Late-Stage Ionis-Owned Programs</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Donidalorsen and PKK</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe donidalorsen is protected from generic competition in the U.S. and Europe until at least 2035. Additional patent applications
    to protect donidalorsen in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting donidalorsen in the U.S. and Europe.</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">United States</span></div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,315,811</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS FOR MODULATING KALLIKREIN (KLKB1) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating HAE</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2717923</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS FOR MODULATING KALLIKREIN (KLKB1) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Compounds for use in treating an inflammatory condition, including HAE</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,294,477</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING PKK EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of donidalorsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3137091</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING PKK EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of donidalorsen</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Zilganersen and GFAP</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe zilganersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> is protected from generic competition
      in the U.S. until at least 2041. </span>A patent application designed to protect zilganersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>from generic competition is being pursued in Europe; a patent issuing
    from that application would have term until at least 2041. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The table below lists a key issued patent protecting </span>zilganersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in the U.S. and a pending application in Europe:</span></div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Patent Application No.)</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,786,546</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOUNDS AND METHODS FOR MODULATING GFAP</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2041</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of zilganersen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(20846055.0)</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOUNDS AND METHODS FOR MODULATING GFAP</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2041</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of zilganersen</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">ION582 and UBE3A</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe ION582<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> is protected from generic competition in
      the U.S. until at least 2040. </span>A patent application designed to protect ION582<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>from generic competition is being pursued in Europe; a patent issuing from that
    application would have term until at least 2040. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The table below lists a key issued patent protecting </span>ION582<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in the U.S. and Europe:</span></div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,261,446</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOUNDS AND METHODS FOR MODULATING UBE3A-ATS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2040</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of ION582</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,617,539</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF UBE3A-ATS EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating Angelman syndrome with an antisense compound targeting a region of UBE3A-ATS</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3770258</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF UBE3A-ATS EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides complementary to a region of UBE3A-ATS for use in treating Angelman syndrome</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Late-Stage Partnered Programs</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Bepirovirsen and Hepatitis B Virus</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe bepirovirsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> is protected from generic competition
      in the U.S. and Europe until at least 2032. Additional patent protection designed to protect bepirovirsen in other foreign jurisdictions is being pursued. With GSK&#8217;s license of bepirovirsen, we assigned our interest in these patents to GSK. The table
      below lists some key issued patents protecting </span>bepirovirsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in the U.S. and Europe:</span></div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; margin-right: 3.25pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,642,752</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF HEPATITIS B VIRUS (HBV) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of bepirovirsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3505528</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF HEPATITIS B VIRUS (HBV) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of bepirovirsen</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Pelacarsen and Apo(a)</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe pelacarsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> is protected from generic competition
      in the U.S. and Europe until at least 2034. Additional patent protection designed to protect pelacarsen in other foreign jurisdictions is being pursued. The table below lists some key issued patents protecting </span>pelacarsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in the U.S. and Europe:</span></div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,574,193</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Methods of lowering Apo(a) and/or Lp(a) levels with an oligonucleotide
              complementary within the nucleotide region of Apo(a) targeted by p</span>elacarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,478,448</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Methods of treating hyperlipidemia with an oligonucleotide complementary
              within the nucleotide region of Apo(a) targeted by p</span>elacarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,884,072</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides complementary within the nucleotide region of Apo(a) targeted by pelacarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2855500</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides complementary within the nucleotide region of Apo(a) targeted by pelacarsen for decreasing Apo(a) expression</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,181,550</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN (a) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Composition of p</span>elacarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2992009</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN (a) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of pelacarsen</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Sefaxersen and Factor B</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe sefaxersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> is protected from generic competition
      in the U.S. and Europe until at least 2035. Additional patent protection designed to protect </span>sefaxersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in other foreign jurisdictions is being pursued. The table
      below lists some key issued patents protecting </span>sefaxersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in the U.S. and Europe:</span></div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3043827</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATORS OF COMPLEMENT FACTOR B</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Compound comprising the antisense oligonucleotide portion of </span>sefaxersen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,280,423</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING COMPLEMENT FACTOR B EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Composition of </span>sefaxersen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3137596</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING COMPLEMENT FACTOR B EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Composition of </span>sefaxersen</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Ulefnersen and FUS</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patent applications designed to protect ulefnersen from generic competition are being pursued in the U.S. and Europe. Patents issued from
    these applications would have terms until at least 2040. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The table below lists some key pending patent applications designed to protect ulefnersen</span> in the U.S. and
    Europe:</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Jurisdiction</span></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Application No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17/613,183</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOUNDS AND METHODS FOR REDUCING FUS EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2040</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of ulefnersen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20815459.1</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOUNDS AND METHODS FOR REDUCING FUS EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2040</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of ulefnersen</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Platform IP</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to the IP that provides exclusivity for specific products, we also pursue IP that provides exclusivity for our core technology
    in the field of oligonucleotides and RNA-targeting therapeutics more generally. Our core technology patents include claims to chemically modified oligonucleotides as well as designs utilizing these chemical modifications. Because these core claims are
    independent of specific therapeutic target, nucleic acid sequence, or clinical indication, they may reach several products.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Chemically Modified Nucleosides and Oligonucleotides</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The most broadly applicable of our patents are those that claim modified nucleosides and oligonucleotides comprising the modified
    nucleosides that we incorporate into our medicines to increase their therapeutic efficacy. The following are some of our patents in this category in the U.S. and Europe:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,399,845</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cEt nucleosides and oligonucleotides containing these nucleoside analogs</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,741,457</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cEt nucleosides and oligonucleotides containing these nucleoside analogs</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,022,193</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides containing cEt nucleoside analogs</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1984381</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cEt nucleosides and oligonucleotides containing these nucleoside analogs</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2314594</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides containing cEt nucleoside analogs and methods of use</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,569,686</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOUNDS AND METHODS FOR SYNTHESIS OF BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of synthesizing cEt nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2092065</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having 2&#8217;-modifed and LNA nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2410053</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having wings comprised of 2&#8217;-MOE and bicyclic nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2410054</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having a 2&#8217;-modifed nucleoside in the 5&#8217;-wing and a bicyclic nucleoside in the 3&#8217;-wing</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,550,988</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2028</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having BNA nucleosides and 2&#8217;-MOE nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,493,092</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2028</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having BNA nucleosides and 2&#8217;-MOE nucleosides and/or 2&#8217;-OMe nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3067421</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">OLIGOMERIC COMPOUNDS COMPRISING BICYCLIC NUCLEOTIDES AND USES THEREOF</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having at least one bicyclic, one 2&#8217;-modified nucleoside and one 2&#8217;-deoxynucleoside</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,629,348</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">LINKAGE MODIFIED OLIGONUCLEOTIDES AND USES THEREOF</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2040</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having 2-4 mesyl phosphoramidate internucleoside linkages at specified positions in the gap</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">LIgand-Conjugated Antisense (LICA) Technology</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have patent claims to new chemistries created to enhance targeting of antisense medicines to specific tissues and cells to improve
    a drug&#8217;s properties. We designed our GalNAc LICA medicines to provide an increase in potency for targets in the liver. We have successfully obtained issued patent claims covering our LICA technology conjugated to any modified oligonucleotide, including
    gapmers, double-stranded siRNA compounds, and fully modified oligonucleotides. The following patents are some examples of our issued patents in this category:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 31%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,127,276</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Preferred THA LICA conjugated to any group of nucleosides, including gapmers, double-stranded siRNA compounds, and fully modified oligonucleotides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,181,549</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Preferred THA conjugate having our preferred linker and cleavable moiety conjugated to any oligomeric compound or any nucleoside having a 2&#8217;-MOE
            modification or a cEt modification</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2991661</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Preferred THA LICA conjugated to any group of nucleosides, including gapmers, double-stranded siRNA compounds, and fully modified oligonucleotides</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Manufacturing</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also own patents claiming methods of manufacturing and purifying oligonucleotides and related compounds. These patents claim methods
    for improving oligonucleotide drug manufacturing, including processes for large-scale oligonucleotide synthesis and purification.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Government Regulation</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 35pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Regulation by government authorities in the U.S. and other countries is a significant component in the development, manufacture and
    commercialization of pharmaceutical products and services. In addition to regulations enforced by the FDA and relevant foreign regulatory authorities, we are also subject to regulation under the Occupational Safety and Health Act, the Environmental
    Protection Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act and other present and potential future federal, state and local regulations.</div>

  <div style="text-align: justify; text-indent: 35pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Extensive regulation by the U.S. and foreign governmental authorities governs the development, manufacture and sale of our medicines. In
    particular, our medicines are subject to a number of approval requirements by the FDA in the U.S. under the Federal Food, Drug and Cosmetic Act, or FDCA, and other laws and by comparable agencies in those foreign countries in which we conduct business.
    The FDCA and other various federal, state and foreign statutes govern or influence the research, testing, manufacture, safety, labeling, storage, recordkeeping, approval, promotion, marketing, distribution, post-approval monitoring and reporting,
    sampling, quality, and import and export of our medicines. State, local, and other authorities also regulate pharmaceutical manufacturing facilities and procedures.</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our manufacturing facility and our CMOs are subject to periodic inspection by the FDA and other foreign equivalents to ensure that they
    are operating in compliance with cGMP requirements. In addition, marketing authorization for each new medicine may require a rigorous manufacturing pre-approval inspection by regulatory authorities. Post approval, there are strict regulations regarding
    changes to the manufacturing process, and, depending on the significance of the change, changes may require prior FDA approval. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation
    requirements upon us and any third-party manufacturers that we may decide to use.</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA must approve any new medicine before a manufacturer can market it in the U.S. In order to obtain approval, we and our partners
    must complete clinical studies and prepare and submit an NDA to the FDA. If the FDA approves a medicine, it will issue an approval letter authorizing commercial marketing of the medicine and may require a risk evaluation and mitigation strategy, or
    REMS, to help ensure the benefits of the medicine outweigh the potential risks. The requirements for REMS can materially affect the potential market and profitability of our medicines. In foreign jurisdictions, the drug approval process is similarly
    demanding.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Pricing and Reimbursement</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For any approved medicine, domestic and foreign sales of the medicine depend, in part, on the availability and amount of coverage and
    adequate reimbursement by third-party payers, including governments and private health plans. The process for determining whether a payer will provide coverage for a product may be separate from the process for setting the reimbursement rate that the
    payer will pay for the product, or procedures that utilize such product. Private health plans may seek to manage cost and use of our medicines by implementing coverage and reimbursement limitations. For example, third-party payers may limit coverage to
    specific products on an approved list, or formulary, which might not include all FDA-approved products for a particular indication. Moreover, a payer&#8217;s decision to provide coverage for a medicine does not imply that an adequate reimbursement rate will
    be approved. Additionally, coverage and reimbursement for drugs can differ significantly from payer to payer. One third-party payer&#8217;s decision to cover a particular medicine does not ensure that other payers will also provide coverage for the medicine
    or will provide coverage at an adequate reimbursement rate.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Third-party payers are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medicines and
    services, in addition to their safety and efficacy. To obtain coverage and reimbursement for any medicine that might be approved for sale, we may need to conduct expensive pharmacoeconomic studies to demonstrate the medical necessity and
    cost-effectiveness of our medicine. These studies will be in addition to the studies required to obtain regulatory approvals. If third-party payers do not consider a medicine to be cost-effective compared to other available therapies, they may not
    cover the medicine after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to sell such medicine at a profit.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In certain jurisdictions, governments may also regulate or influence coverage, reimbursement and/or pricing of our medicines to control
    cost or affect use. In the European community, governments influence the price of drugs through their pricing and reimbursement rules and control of national health care systems that fund a large part of the cost of those medicines to consumers. Some
    jurisdictions operate positive and negative list systems under which medicines may only be marketed once a reimbursement price has been agreed to by the government. To obtain reimbursement or pricing approval, some of these countries may require the
    completion of clinical studies that compare the cost effectiveness of a particular drug candidate to currently available therapies. Other member states allow companies to fix their own prices for medicines but monitor and control company profits.</div>

  <div><br/>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The marketability of any medicine for which we receive regulatory approval for commercial sale may suffer if the government or third-party
    payers fail to provide adequate coverage and reimbursement. In addition, the focus on cost containment measures in the U.S. and other countries has increased and we expect will continue to increase the pressure on pharmaceutical pricing. Coverage
    policies and third-party reimbursement rates may change at any time. Even if we attain favorable coverage and reimbursement status for one or more medicines for which we receive regulatory approval, less favorable coverage policies and reimbursement
    rates may be implemented in the future.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Healthcare Reform</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Both the federal and state governments in the U.S. and foreign governments continue to propose and pass new legislation and regulations
    designed to contain or reduce the cost of healthcare.</div>

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    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There has also been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which
    has resulted in efforts to bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for medicines. For example, in August 2022, the
    Inflation Reduction Act of 2022, or the IRA, was signed into law, which includes key actions aimed at reducing the costs of prescription drugs and allows HHS to negotiate the price of certain single-source drugs covered under Medicare and establish a
    price cap on such drugs, known as the Maximum Fair Price. There are important exemptions to the Maximum Fair Price, including for medications that are orphan drug designated and approved for only one rare disease, and drugs with low Medicare spend as
    defined by the Centers for Medicare &amp; Medicaid Services.&#160; The IRA, among other things, (1) directs the U.S. Department of Health and Human Services, or HHS, to negotiate, through a negotiation program, the price of certain single-source drugs and
    biologics that have been on the market for at least seven years covered under Medicare, or the Medicare Drug Price Negotiation Program, and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace
    inflation. These provisions began to take effect progressively starting in fiscal year 2023, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges. Under this program, HHS has already announced the agreed-upon
    prices of the first drugs that were subject to price negotiations and will announce the agreed-upon prices of additional drugs in the coming years. In response to an October 2022 executive order, on February 14, 2023, HHS released a report outlining
    three new models for testing by the CMS Innovation Center, which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care. It is unclear whether the models will be utilized in any health reform
    measures in the future. Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs using march-in rights under the Bayh-Dole Act. On December 8, 2023, the National Institute of Standards
    and Technology, or NIST, published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise
    march-in rights. While march-in rights have not previously been exercised, it is uncertain if that will continue under the new NIST framework, if such framework is finalized. Further, additional health reform measures may be implemented in the future,
    particularly in light of the recent U.S. presidential and congressional elections.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payments from private
    payers.&#160; Our future product sales may be subject to additional discounts from list price in the form of rebates and discounts provided to 340B covered entities. Changes to the 340B program or to Medicare or Medicaid programs at the federal or state
    level, including outcomes of ongoing litigation in our industry, may impact our product prices and rebate liability.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, the distribution of prescription pharmaceutical products is subject to the Drug Supply Chain Security Act, or DSCA, which
    regulates the distribution and tracing of prescription drugs and prescription drug samples at the federal level and sets minimum standards for the regulation of drug distributors by the states. The DSCA imposes requirements to ensure accountability in
    distribution and to identify and remove counterfeit and other illegitimate products from the market.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other healthcare laws that may affect our ability to operate include, for example, the following:</div>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act,
            which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign and state laws governing the privacy and security of health information, such as the General Data Protection Regulation, or GDPR, in the EU and UK; and the
            California Consumer Privacy Act, or CCPA, in California, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect; and</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The Physician Payments Sunshine Act, which requires manufacturers of medicines, devices, biologics, and medical supplies to report annually to the Centers for Medicare
            and Medicaid Services information related to payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), other healthcare providers (such as physician assistants and
            nurse practitioners), and teaching hospitals, and ownership and investment interests held by physicians and their immediate family members.</div>
        </td>

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    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Sales and Marketing</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Numerous regulatory authorities in addition to the FDA, including, in the U.S., the Centers for Medicare and Medicaid Services, other
    divisions of the HHS, the U.S. Department of Justice, and similar foreign, state and local government authorities, regulate sales, promotion and other activities following drug approval. As described above, the FDA regulates all advertising and
    promotion activities for drugs under its jurisdiction both prior to and after approval. Only those claims relating to safety and efficacy that the FDA has approved may be used in labeling. Physicians may prescribe legally available drugs for uses that
    are not described in the drug&#8217;s labeling and that differ from those tested and that the FDA approved. The FDA does not regulate the behavior of physicians in their choice of treatments, but FDA regulations do impose stringent restrictions on
    manufacturers&#8217; communications regarding off-label uses. If we do not comply with applicable FDA requirements, we may face adverse publicity, enforcement action by the FDA, including corrective advertising, consent decrees and the full range of civil
    and criminal penalties available to the FDA. Promotion of off-label uses of drugs can also implicate the false claims laws described below.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the U.S., sales, marketing and scientific/educational programs must also comply with various federal and state laws pertaining to
    healthcare &#8220;fraud and abuse,&#8221; including anti-kickback laws and false claims laws. Anti-kickback laws make it illegal for a prescription drug manufacturer to solicit, offer, receive, or pay any remuneration in exchange for, or to induce, the referral of
    business, including the purchase or prescription of a particular drug. Despite our best efforts to comply with applicable law and regulations, due to the breadth of the statutory provisions, limited statutory exceptions and regulatory safe harbors, and
    the absence of guidance in the form of regulations and very few court decisions addressing industry practices, it is possible that our practices might be challenged under anti-kickback or similar laws. Moreover, healthcare reform legislation has
    strengthened these laws. For example, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or Affordable Care Act, among other things, amends the intent requirement of the federal
    anti-kickback and criminal healthcare fraud statutes to clarify that a person or entity does not need to have actual knowledge of this statute or specific intent to violate it. In addition, the Affordable Care Act clarifies that the government may
    assert that a claim that includes items or services resulting from a violation of the federal anti-kickback statute constitutes a false or fraudulent claim for purposes of the false claims statutes. False claims laws prohibit anyone from knowingly and
    willingly presenting, or causing to be presented for payment, to third-party payers (including Medicare and Medicaid) claims for reimbursed drugs or services that are false or fraudulent, claims for items or services not provided as claimed, or claims
    for medically unnecessary items or services. Our activities relating to the sale and marketing of our drugs may be subject to scrutiny under these laws. Violations of fraud and abuse laws may be punishable by criminal and civil sanctions, including
    fines and civil monetary penalties, the possibility of exclusion from federal healthcare programs (including Medicare and Medicaid) and corporate integrity agreements, which impose, among other things, rigorous operational and monitoring requirements
    on companies. Similar sanctions and penalties also can be imposed upon executive officers and employees, including criminal sanctions against executive officers under the so-called &#8220;responsible corporate officer&#8221; doctrine, even in situations where the
    executive officer did not intend to violate the law and was unaware of any wrongdoing.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Given the significant penalties and fines that can be imposed on companies and individuals if convicted, allegations of such violations
    often result in settlements even if the company or individual being investigated admits no wrongdoing. Settlements often include significant civil sanctions, including fines and civil monetary penalties, corporate integrity agreements, and could
    include criminal penalties. If the government alleged, or subsequently settled or convicted us or our executive officers of violating these laws, our business could be harmed. In addition, private individuals can bring similar actions. Our activities
    could be subject to challenge for the reasons discussed above and due to the broad scope of these laws and the increasing attention being given to them by law enforcement authorities. As described above, other healthcare laws that may affect our
    operations include HIPAA, analogous state laws governing the privacy and security of health information, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, and the
    Physician Payments Sunshine Act. Further, there are an increasing number of state laws that require manufacturers to make reports to states on pricing and marketing information. Many of these laws contain ambiguities as to what is required to comply
    with the laws. Given the lack of clarity in laws and their implementation, our reporting actions could be subject to the penalty provisions of the pertinent state authorities.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Similar rigid (and in some areas, heightened) restrictions are imposed on the promotion and marketing of drugs in the E.U. and other
    countries. Even in those countries where we may not be directly responsible for the promotion and marketing of our medicines, if our potential international distribution partners engage in inappropriate activity, it can have adverse implications for
    us.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed above, both the federal and state governments in the U.S. and foreign governments continue to propose and pass new
    legislation and regulations designed to contain or reduce the cost of healthcare, including new models aimed to lower of cost of drugs, promote accessibility, and improve quality of care and initiatives to control the price of prescription drugs using
    march-in rights under the Bayh-Dole Act.</div>

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    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">The Foreign Corrupt Practices Act</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The U.S. Foreign Corrupt Practices Act, or FCPA, prohibits certain individuals and entities, including us, from promising, paying,
    offering to pay, or authorizing the payment of anything of value to any foreign government official, directly or indirectly, to obtain or retain business or an improper advantage. The FCPA also requires publicly traded companies to maintain accurate
    books and records and establish and maintain a system of internal accounting controls. If we violate the FCPA, it could result in large civil and criminal penalties as well as have an adverse effect on our reputation, operations, and financial
    condition. We could also face collateral consequences such as debarment and the loss of export privileges. In addition, in many other countries, the healthcare providers who conduct clinical trials or prescribe pharmaceuticals are employed by their
    government, and the purchasers of pharmaceuticals are government entities; therefore, any dealings with these prescribers and purchasers may be subject to regulation under the FCPA. There is no certainty that all employees and third-party business
    partners (including our contract research organizations, contract manufacturing organizations, distributors, wholesalers, agents, contractors and other partners) will comply with the FCPA or local anti-bribery laws. Importantly, we do not control the
    actions of manufacturers and other third-party agents, although we may be liable for their actions.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Competition</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Our Business in General</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Some of our medicines may compete with existing therapies for market share and some of our medicines in development may compete for
    patients in clinical trials. In addition, there are a number of companies pursuing the development of genetic medicines and the development of pharmaceuticals utilizing these technologies. These companies include biopharmaceutical companies and large
    pharmaceutical companies acting either independently or together. Our medicines are differentiated from traditional small molecule medicines by their chemistry, how they move in the body, how they act in the body, delivery technology, and formulations.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our commercial medicines and our medicines in development address numerous markets. The diseases our medicines target for which we have or
    may receive marketing authorization will determine our competition. For some of our medicines, an important factor may be the timing of market introduction of competitive products. Accordingly, the relative speed with which we can develop medicines,
    complete the clinical trials and marketing authorization processes and supply commercial quantities of the medicines to the market are important competitive factors. We expect to compete with products approved for sale based on a variety of factors,
    including, among other things, product efficacy, safety, mechanism of action, dosing administration, marketing and sales strategy and tactics, availability, price, and reimbursement.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Below we have included what we believe to be medicines that compete or may compete directly with our marketed medicines and late-stage
    medicines. We included competitors and potential competitors that are past Phase 1 development.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Marketed Medicines</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">TRYNGOLZA/Olezarsen and WAYLIVRA</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We believe that the following medicines could compete with </span>TRYNGOLZA/olezarsen







    and WAYLIVRA<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in FCS and sHTG:</span></div>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ARO-APOC3</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Plozasiran)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Arrowhead</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Targets APOCIII by utilizing Targeted RNAi Molecule Platform</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Submitted in US for FCS,</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 sHTG</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pegozafermin</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">89bio</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">FGF21 analog</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 sHTG</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

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  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NST-1024</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NorthSea Therapeutics</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CETP Inhibitor</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2a</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

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  </div>

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  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

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</table>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">WAINUA/Eplontersen and TEGSEDI</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider the following medicines as competitors and potential future competitors to WAINUA/eplontersen and TEGSEDI for ATTRv-PN and/or
    ATTR-CM:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 18%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Onpattro</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Patisiran)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Alnylam</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An RNAi medicine formulated with lipid nanoparticles to inhibit TTR mRNA</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved in US, EU, Japan and select other markets for ATTRv-PN</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vyndaqel/Vyndamax</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Tafamidis and tafamidis meglumine)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pfizer</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A small molecule medicine to stabilize TTR protein</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved in EU, Japan and select other markets for ATTRv-PN (not approved in the US); ATTR-CM approved in the US, EU and other geographies</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amvuttra</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Vutrisiran)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Alnylam</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An RNAi medicine conjugated with GalNAc to inhibit TTR mRNA</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for ATTRv-PN in the US, EU and Japan; Submitted in US, EU for ATTR-CM</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Attruby (Acoramidis)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">BridgeBio</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Small molecule that binds and stabilizes TTR in the blood</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved in US; Submitted in EU and Japan</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NTLA-2001 (Nexiguran Ziclumeran (nex-z))</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intellia/ Regeneron</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CRISPR therapeutic candidate designed to reduce circulating TTR protein levels</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 ATTR-CM,</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 ATTRv-PN</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ALXN2220</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AstraZeneca</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A monoclonal IgG1 which acts by depleting TTR protein</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 ATTR-CM</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NNC6019-0001</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novo Nordisk</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A monoclonal antibody to deplete amyloid</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 ATTR-CM</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider the following medicines as competitors to SPINRAZA for the indication of SMA:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 18%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Zolgensma</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Onasemnogene abeparvovec)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gene therapy targeting the genetic root cause of SMA by replacing the missing or nonworking SMN1 gene</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for pediatric SMA patients less than 2 years of age</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Evrysdi</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Risdiplam)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Roche</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A small molecule medicine that modulates splicing of the SMN2 gene</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for SMA in pediatric and adult patients</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">OAV101</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Onasemnogene abeparvovec)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gene therapy targeting the genetic root cause of SMA by replacing the missing or nonworking SMN1 gene</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intrathecal Injection</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

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  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32</div>

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      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">QALSODY</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the following medicine could compete with QALSODY in SOD1-ALS:</div>

  <div><br/>
  </div>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

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    <td style="width: 18%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NI-005 / AP-101</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Neurimmune (AL-S Pharma) / Lilly</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A human derived antibody targeting misfolded SOD1</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

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</table>
  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Late-Stage Ionis-Owned Programs</div>

  <div><br/>
  </div>

  <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Donidalorsen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the following medicines could compete with donidalorsen as a prophylactic treatment for patients with HAE:</div>

  <div><br/>
  </div>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

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    <td style="width: 18%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Takhzyro</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(lanadelumab-flyo)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Takeda</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A monoclonal antibody that inhibits plasma kallikrein activity</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for HAE patients two years and older</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cinryze</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(C1 esterase inhibitor)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Takeda</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A human plasma protein that mediates inflammation and coagulation</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for HAE patients six years and older</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Orladeyo</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(berotralstat)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">BioCryst</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral plasma kallikrein inhibitor</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for HAE patients 12 years and older</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Haegarda</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(C1 esterase inhibitor)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CSL Behring</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">C1 esterase inhibitor</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for HAE patients 6 years and older</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Garadacimab</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CSL Behring</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An anti-factor XIIa monoclonal antibody</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for HAE patients 12 years and older in Australia and the UK</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">EC Decision Pending in EU; Received CRL in the US</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deucrictibant</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pharvaris</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An oral B2-receptor antagonist</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NTLA-2002</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intellia</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CRISPR therapeutic candidate designed to inactivate the kallikrein B1 gene</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">STAR-0215 (Navenibart)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Astria</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A monoclonal antibody inhibitor of plasma kallikrein</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Zilganersen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe there are no medicines in clinical development for AxD.</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">ION582</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the following medicines could compete with ION582 in Angelman syndrome:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 18%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">GTX-102</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ultragenyx Pharma</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An ASO designed to inhibit expression of UBE3A-ATS</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intrathecal</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Alogabat</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Roche</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A small molecule that is GABA A alpha 5 receptor modulator</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NNZ-2591</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Neuren Pharmaceuticals</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A small molecule, cGP analog, that targets IGF-1</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Late-Stage Partnered Programs</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bepirovirsen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the following medicines could compete with bepirovirsen in HBV</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elebsiran</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(VIR-2218)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vir Biotech / Alnylam</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RNAi therapeutic to reduce HBV viral antigens</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Imdusiran</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(AB-729)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Arbutus Biopharma</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RNAi therapeutic to reduce HBV viral antigens</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tobevibart</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(VIR-3434)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vir Biotech</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Monoclonal antibody neutralizing hepatitis B virus</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selgantolimod</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gilead Sciences</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Toll-like receptor 8 agonist</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Bersacapavir</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Johnson &amp; Johnson</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Capsid assembly modulator</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">REP 2139-Mg</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Replicor Inc.</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Nucleic acid polymer that blocks the assembly of subviral particles (SVPs) in hepatocytes</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion / Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">VTP-300</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Barinthus Bio</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antigen-specific immunotherapy</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intramuscular Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">BRII-179</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brii Biosciences</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Recombinant protein-based immunotherapy</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intramuscular Injection</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Pelacarsen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the following medicines could compete with pelacarsen in CVD in patients with elevated LP(a):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olpasiran</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amgen/ Arrowhead</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RNAi therapeutic designed to lower Lp(a)</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lepodisiran</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lilly</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RNAi therapeutic designed to lower Lp(a)</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Zerlasiran</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Silence</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RNAi therapeutic designed to lower Lp(a)</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Muvalaplin</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lilly</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Small molecule therapy to lower Lp(a)</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Sefaxersen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We believe that the following medicines could compete with</span>
    sefaxersen <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in IgAN:</span></div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 18%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tarpeyo (budesonide)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Asahi Kasei (Calliditas)</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A corticosteroid indicated to reduce proteinuria in adults with primary IgAN</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for IgAN</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Filspari<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><br/>
            </span>(Sparsentan)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Travere</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An endothelin &amp; angiotensin II receptor antagonist to reduce proteinuria in adults with primary IgAN</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for IgAN</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Fabhalta</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Iptacopan)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis (Chinook)</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A factor B inhibitor of the alternative complement pathway</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for IgAN</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Atrasentan</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis (Chinook)</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An endothelin A receptor antagonist</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN); Submitted in US for accelerated approval</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Zigakibart</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis (Chinook)</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An anti-APRIL monoclonal antibody</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sibeprenlimab</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Otsuka (Visterra)</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A humanized IgG2 monoclonal antibody that inhibits APRIL</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Atacicept</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vera</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A recombinant fusion protein a dual inhibitor of BLyS and APRIL</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ravulizumab</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Alexion (AstraZeneca)</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A humanized monoclonal antibody to complement factor 5</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Povetacicept</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Alpine Immune Sciences</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A dual BAFF and APRIL inhibitor</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion / Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Telitacicept</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RemeGen</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A dual BAFF and APRIL inhibitor</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vemircopan</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Alexion (AstraZeneca)</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A complement factor D inhibitor</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 (IgAN)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Felzartamab</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Hi-Bio</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A monoclonal antibody directed against CD38</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 (IgAN)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

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</table>
  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ulefnersen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe there are no medicines in clinical development for FUS-ALS.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Corporate Responsibility Initiatives</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe operating responsibly and sustainably creates long-term value for our company and our stakeholders. We recognize the importance
    of Corporate Responsibility, or CR, and Environmental, Social and Governance, or ESG, initiatives as it relates to our business strategy and risk assessment. We continue to evolve our CR program and established three strategic CR pillars and associated
    goals in 2023 to guide our approach and provide a framework for reporting on our performance. </div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We began reporting on CR metrics in 2021 and have continued to expand disclosure since then. In 2024, we reported progress on our CR goals
    aligned to the three strategic CR pillars that we believe are most important to our business:</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis Corporate Responsibility Strategic Pillars</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 33.33%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Innovate to improve the lives </div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of people with serious diseases</div>
        </td>

    <td style="width: 34%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Empowering our</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">employees and communities</div>
        </td>

    <td style="width: 33.33%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Operating</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">responsibly and sustainably</div>
        </td>

  </tr>

  <tr>

    <td style="width: 33.33%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We innovate across the business and work tirelessly to discover, develop and deliver important new medicines for
            people with serious diseases.</div>
        </td>

    <td style="width: 34%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; margin-left: 4.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We are committed to fostering an inclusive culture that drives excellence, embraces diversity, and supports our
            communities.</div>
        </td>

    <td style="width: 33.33%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We operate with integrity to help create a better, more sustainable future for all through environmental
            stewardship and responsible business practices and stakeholder interactions.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 33.33%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #FFFFFF;">
          <div style="text-indent: 4.5pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt" class="TRGRRTFtoHTMLTab">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Innovation and R&amp;D</span></div>
          <div style="text-indent: 4.5pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt" class="TRGRRTFtoHTMLTab">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Access and Affordability</span></div>
          <div style="text-indent: 4.5pt;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 12pt;">&#8226;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt" class="TRGRRTFtoHTMLTab">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Patient Advocacy and Engagement</span></div>
        </td>

    <td style="width: 34%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(255, 255, 255);">
          <div style="text-indent: 4.2pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt" class="TRGRRTFtoHTMLTab">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Workplace Culture, Talent Attraction and Development</span></div>
          <div style="text-indent: 4.2pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt" class="TRGRRTFtoHTMLTab">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Inclusion and Belonging</span></div>
          <div style="text-indent: 4.2pt;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 12pt;">&#8226;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt" class="TRGRRTFtoHTMLTab">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Social Impact and Community Engagement</span></div>
        </td>

    <td style="width: 33.33%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #FFFFFF;">
          <div style="text-indent: 4.5pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt" class="TRGRRTFtoHTMLTab">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Environmental Sustainability</span></div>
          <div style="text-indent: 4.5pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt" class="TRGRRTFtoHTMLTab">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Governance and Integrity</span></div>
          <div style="text-indent: 4.5pt;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 12pt;">&#8226;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt" class="TRGRRTFtoHTMLTab">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Data Privacy and Cybersecurity</span></div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our CR initiatives are driven by our Chief Executive Officer and executive-level CR Steering Committee, or CR Committee. The CR Committee
    consists of senior leaders in key functions across the company, including legal, finance, investor relations, human resources, research and development, manufacturing, commercial, compliance and corporate affairs.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The CR Committee is part of our governance framework, which defines responsibilities and ensures we have the right systems and controls to
    oversee ethical and sustainable operations across our business. Our Board of Directors, specifically the Nominating, Governance and Review Committee, has oversight of our overall CR strategy and material CR risks and opportunities as outlined in the
    Committee&#8217;s charter. The Board receives updates related to corporate governance and corporate responsibility from the CR Committee at least once annually. We look to our stakeholders and third-party frameworks such as the Sustainability Accounting
    Standards Board Health Care &#8211; Biotechnology and Pharmaceuticals Standard and the Task Force on Climate-Related Financial Disclosures to inform our approach and our disclosures.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We will share progress on our CR goals and more details on our initiatives in our 2024 CR Report, which we expect to publish in April 2025
    and available on our website. Nothing in the report or on our website shall be deemed incorporated by reference into this Annual Report on Form 10-K.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Employees and Human Capital</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of February 13, 2025, we
    employed 1,069 people, the vast majority of whom reside in the U.S. A significant number of our management and professional employees have had prior experience with pharmaceutical, biotechnology or medical product companies. Our average employee
    turnover rate in 2023 was 6 percent, while the turnover for life sciences and medical device companies over this period was 21 percent according to a survey published by Radford &#8211; an Aon Hewitt Company. Given the uniqueness and complexity of our
    technology, it is critical to retain the knowledge and experience of outstanding long service employees. The experience and seniority of our employees is as critical to our future success as it has been to the success we have enjoyed to date.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collective bargaining agreements do not cover any of our employees, and management considers relations with our employees to be good. We
    believe that the future will be defined by outstanding people and we are committed to recruiting, developing, motivating, and rewarding them.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We encourage you to visit our website for more detailed information regarding our Human Capital programs and initiatives. Nothing on our
    website shall be deemed incorporated by reference into this Annual Report on Form 10-K.</div>

  <div><br/>
  </div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">36</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Benefits</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reward our employees individually on the basis of their responsibilities and accomplishments. We offer competitive compensation and
    benefits to our employees. In addition to salary and bonus programs, we also offer:</div>

  <div><br/>
  </div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Comprehensive medical, dental and vision insurance;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">401(k) matching;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock options, RSUs and an Employee Stock Purchase Plan, or ESPP;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vacation, holiday, sick time and paid time off for volunteering;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Wellness programs;</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Flexible spending accounts for health and dependent day care needs;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Family care benefits;</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Life, AD&amp;D insurance and long-term disability insurance coverage options; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Assistance Program, or EAP.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize achievements with salary increases, equity awards, promotions, and bonus opportunities.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Pay Equity</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are committed to paying our employees fairly, regardless of their gender, ethnicity, race, age or other personal characteristics. To
    ensure we are achieving our commitment, we benchmark and evaluate pay based on market data and consider factors such as an employee&#8217;s role and experience, an employee&#8217;s performance and internal equity. We also regularly review our compensation
    practices, in terms of our overall workforce and individual employees, to ensure our pay is fair and equitable.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On an annual basis, we monitor our pay equity status and market competitiveness, and perform a pay equity analysis that reviews pay equity
    by gender, ethnicity, race and age. Our 2024 pay equity analysis confirmed we do not have a statistically significant difference in pay for the same or similar work, regardless of gender, ethnicity, race or age.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">A Culture of Inclusion</div>

  <div><br/>
  </div>

  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At Ionis, prejudicial barriers to human potential and productivity are foreign to our values. We recognize that for the full potential
      of our workforce to be realized, we must cultivate an inclusive culture where all employees feel empowered to contribute fully in an environment that values different perspectives, leading to better &#8203;&#8203;&#8203;&#8203;&#8203;&#8203;&#8203;ideas and increased innovation. We have
      several employee-led resource groups dedicated to supporting engagement and empowerment and a diverse management team and board of directors. From our Executive Leadership Team to our newest hire, we strive for an environment where our employees feel
      a strong sense of belonging in our organization.</div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Training and Development</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We designed our training and development programs to help employees gain important Ionis knowledge and develop the skills to be successful
    at Ionis. All of our trainings from new hire through senior leader, are focused on the Ionis culture and core principles and learning what we mean when we say: &#8220;Working the Ionis Way.&#8221;</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We empower our employees to build rewarding careers at Ionis, driven by a culture of having a bias to act that encourages personal and
    professional employee growth. Ionis offers robust training opportunities with course offerings and events available to every employee regardless of level or function. In addition, employees also have access to Ionis&#8217; learning and development library
    that houses important information on career growth and planning. By supporting our employees, we know that each professional development milestone enables our continued success.</div>

  <div><br/>
  </div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Information about our Executive Officers</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following sets forth certain information regarding our executive officers as of February 13, 2025:</div>

  <div style="text-align: left;"><br/>
  </div>

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    <td style="width: 25.83%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Name</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 8.33%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Age</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 62.5%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Position</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia, Ph.D.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Chief Executive Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Joseph T. Baroldi, M.A., M.B.A., M.S.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Business Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brian Birchler</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Corporate and Development Operations</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">C. Frank Bennett, Ph.D.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Scientific Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shannon L. Devers</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Human Resources Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Richard S. Geary, Ph.D.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Development Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elizabeth L. Hougen</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Finance and Chief Financial Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Kyle Jenne</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Global Product Strategy Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patrick R. O&#8217;Neil, Esq.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">51</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Legal Officer, General Counsel and Corporate Secretary</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eugene Schneider, M.D.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Clinical Development and Operations Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eric E. Swayze, Ph.D.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Research</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">BRETT P. MONIA, Ph.D.</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Executive Officer</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 38.15pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Monia was promoted to Chief Executive Officer in January 2020. From January 2018 to December 2019, Dr. Monia served as Chief
    Operating Officer. From January 2012 to January 2018, Dr. Monia served as Senior Vice President. From February 2009 to January 2012, Dr. Monia served as our Vice President, Drug Discovery and Corporate Development and from October 2000 to February
    2009, he served as our Vice President, Preclinical Drug Discovery. From October 1989 to October 2000 he held various positions within our Molecular Pharmacology department.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">JOSEPH T. BAROLDI, M.A., M.B.A., M.S.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Business Officer</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mr. Baroldi has served as Ionis&#8217; Executive Vice President, Chief Business Officer since January 2022. Prior to rejoining Ionis in 2022,
    Mr. Baroldi was the chief operating officer at Avidity Biosciences, a biotechnology company focused on oligonucleotide-based therapies. Prior to Avidity, Mr. Baroldi was Vice President, Business Development at Ionis, where he held several roles of
    increasing responsibility from 2009 to 2020. Mr. Baroldi has also held positions in strategic planning and scientific research for Gen-Probe Inc.</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">BRIAN BIRCHLER</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Corporate and Development Operations</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mr. Birchler has served as Ionis&#8217; Executive Vice President, Corporate and Development Operations since March 2022. From January 2008 to
    March 2022, Mr. Birchler served as our Senior Vice President, Drug Development Operations. From January 2005 to January 2008 he served as our Vice President, Drug Development Operations and from January 2003 to January 2005, as our Vice President,
    Development Chemistry and Operations. Mr. Birchler joined Ionis in 1995 as Senior Scientist/Senior Research Associate. Prior to joining Ionis, Mr. Birchler was employed by CIBA Vision Corp. and Burroughs Wellcome Pharmaceuticals in various engineering,
    development and commercial positions.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">C. FRANK BENNETT, Ph.D.</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Scientific Officer</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Bennett has served as Ionis&#8217; Executive Vice President, Chief Scientific Officer since April 2020. In January 2020, Dr. Bennett was
    promoted to Chief Scientific Officer. From January 2006 to December 2019, Dr. Bennett served as Senior Vice President, Antisense Research. From June 1995 to January 2006, Dr. Bennett served as our Vice President, Research. From March 1993 to June 1995,
    he was Director, Molecular Pharmacology, and from May 1992 to March 1993, he was an Associate Director in our Molecular and Cellular Biology department. Prior to joining Ionis in 1989, Dr. Bennett was employed by SmithKline and French Laboratories in
    various research positions. He is a member of the Board of Directors of the Hereditary Disease Foundation.</div>

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    </div>

  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SHANNON L. DEVERS</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Human Resources Officer</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ms. Devers was promoted to Chief Human Resources Officer in September 2024. From April 2020 to September 2024, Ms. Devers served as our
    Senior Vice President, Human Resources. From August 2013 to March 2020, Ms. Devers served as our Vice President, Human Resources. Ms. Devers joined Ionis in 2001 as Senior Human Resources Manager. Prior to joining Ionis, Ms. Devers was employed by
    Target Corporation, Nike, Inc. and Taco Bell Corporation in various human resources roles.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RICHARD S. GEARY, Ph.D.</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Development Officer</div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Geary has served as Ionis&#8217; Executive Vice President, Chief Development Officer since April 2020. From August 2008 to March 2020, Dr.
    Geary served as our Senior Vice President, Development. From August 2003 to August 2008, Dr. Geary served as our Vice President, Preclinical Development. From November 1995 to August 2003, he held various positions within the Preclinical Development
    department. Prior to joining Ionis in 1995, Dr. Geary was Senior Research Scientist and Group Leader for the bioanalytical and preclinical pharmacokinetics group in the Applied Chemistry Department at Southwest Research Institute.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ELIZABETH L. HOUGEN</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Finance and Chief Financial Officer</div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ms. Hougen has served as Ionis&#8217; Executive Vice President and Chief Financial Officer since April 2020. From January 2013 to March 2020,
    Ms. Hougen served as our Senior Vice President, Finance and Chief Financial Officer. From January 2007 to December 2012, Ms. Hougen served as our Vice President, Finance and Chief Accounting Officer and from May 2000 to January 2007, she served as our
    Vice President, Finance. Prior to joining Ionis in 2000, Ms. Hougen was Executive Director, Finance and Chief Financial Officer for Molecular Biosystems, Inc., a public biotechnology company. She is a member of the Board of Directors and Audit
    Committee chair for Artiva Biotherapeutics.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">KYLE JENNE</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Global Product Strategy Officer</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mr. Jenne has served as Ionis&#8217; Executive Vice President, Chief Global Product Strategy Officer since February 2024. Prior to rejoining
    Ionis in 2024, Mr. Jenne served in senior commercial leadership roles at Ionis and Akcea from May 2017 to August 2022. Prior to joining Akcea in 2017, Mr. Jenne was employed by Schering Plough, King Pharmaceuticals, Acorda Therapeutics and Praecis
    Pharmaceuticals in various commercial roles.</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">PATRICK R. O&#8217;NEIL, Esq.</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Legal Officer, General Counsel and Corporate Secretary</div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mr. O&#8217;Neil has served as Ionis&#8217; Executive Vice President, Chief Legal Officer and General Counsel since September 2021. Mr. O&#8217;Neil also
    serves as our Corporate Secretary. From March 2020 to September 2021, Mr. O&#8217;Neil served as our Executive Vice President, Legal &amp; General Counsel and Chief Compliance Officer. From January 2013 to March 2020, Mr. O&#8217;Neil served as our Senior Vice
    President, Legal and General Counsel. From September 2010 to January 2013, Mr. O&#8217;Neil served as our Vice President, Legal and General Counsel and from January 2009 to September 2010, he served as our Vice President, Legal and Senior Transactions
    Counsel. From October 2001 to January 2009 he held various positions within our Legal department. Prior to joining Ionis, Mr. O&#8217;Neil was an associate at Cooley LLP.</div>

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    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">EUGENE SCHNEIDER, M.D.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Clinical Development and Operations Officer</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Schneider has served as Ionis&#8217; Executive Vice President and Chief Clinical Development and Operations Officer since September 2023.
    From January 2021 to September 2023, Dr. Schneider served as our Executive Vice President and Chief Clinical Development Officer. From August 2018 to December 2020, Dr. Schneider served as our Senior Vice President, Head of Clinical Development. From
    April 2015 to July 2018, Dr. Schneider was our Vice President, Clinical Development, Severe and Rare Diseases. Dr. Schneider joined Ionis in December 2013 as Executive Director, Clinical Development. Dr. Schneider has two decades of experience in
    clinical development primarily in the rare diseases space. Prior to joining Ionis, Dr. Schneider was senior medical director at both Synageva BioPharma and Biovail Technologies Ltd.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ERIC E. SWAYZE, Ph.D.</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Research</div>

  <div><br/>
  </div>

  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Swayze has served as Ionis&#8217; Executive Vice President, Research since April 2020 and is responsible for leading preclinical antisense
      drug discovery and antisense technology research. In January 2020, Dr. Swayze was promoted to Senior Vice President of Research. Previously, Dr. Swayze was Vice President of Chemistry and Neuroscience Drug Discovery at Ionis, overseeing the
      advancement of multiple programs to clinical development. He joined Ionis in 1994 and has contributed to key technology advancements, including Ionis&#8217; Generation 2.5 chemistry and LICA technology.</div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item1A"><!--Anchor--></a>Item 1A. RISK FACTORS</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Investing in our securities involves a high degree of risk. You should carefully consider the following information
    about the risks described below, together with the other information contained in this report and in our other public filings in evaluating our business. If any of the following risks actually occur, our business could be materially harmed, and our
    financial condition and results of operations could be materially and adversely affected. As a result, the trading price of our securities could decline, and you might lose all or part of your investment.</div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the Commercialization of our Medicines</div>

  <div>
    <div><br/>
    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We have limited experience as a company in commercializing medicines and we will have to continue to invest significant resources to
    develop our capabilities. If we are unable to effectively establish and maintain marketing, sales, market access, distribution, and related functions, or enter into agreements with third parties to commercialize our medicines, we may not be able to
    successfully commercialize our medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have historically relied on third parties to commercialize
      our marketed medicines and have limited experience as a company in commercializing medicines. TRYNGOLZA is our first independently launched medicine and we expect to independently launch additional medicines in the future. Any failure to effectively
      commercialize our medicines, including our failure to allocate resources to our commercial launches efficiently or timely, could adversely impact the revenue we generate from our medicines.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If&#160; the commercialization of TRYNGOLZA and future sales are less successful than anticipated by us or our investors or securities analysts, our stock price could decline and our business may be harmed.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We will have to continue to invest significant financial and management resources to build and maintain the infrastructure required to
    successfully commercialize our medicines. We will need to establish and maintain effective sales teams for each of our independently launched medicines and there are significant risks involved in managing a sales organization, including our ability to
    hire, retain and incentivize qualified individuals, generate sufficient sales leads, provide adequate training to sales and marketing personnel, and effectively manage a geographically dispersed sales and marketing team. We must also continue to
    scale-up existing internal support functions to aid our commercialization efforts. Further, these existing support functions will need to work effectively in coordination with new commercial functional areas. Any failure to establish or maintain an
    effective commercialization infrastructure, including our sales, marketing, market access, distribution, and related capabilities, scale-up our existing support functions, or effectively integrate new functional areas, could adversely affect our
    ability to successfully commercialize our medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we choose to rely on third parties to assist us in commercializing our medicines, we may not be able to enter into collaborations or
    hire consultants or external service providers on acceptable financial terms, or at all. In addition, if we continue to engage third parties to assist us in the commercialization of our medicines, our product revenues and profitability may be lower
    than if we commercialized such medicines ourselves.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The proximity of our planned upcoming independent launches could increase the likelihood that such risks will occur.</div>

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    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the market does not accept our medicines, including our commercial medicines and our medicines in development, we are not likely to
    generate substantial revenues or become consistently profitable.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Even if our medicines are authorized for marketing, our success will depend upon the medical community, patients and third-party payers
    accepting our medicines as medically useful, cost-effective, safe and convenient. Even when the FDA or foreign regulatory authorities authorize our or our partners&#8217; medicines for commercialization, doctors may not prescribe our medicines to treat
    patients. Furthermore, we and our partners may not successfully commercialize additional medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, in many of the markets where we or our partners may sell our medicines in the future, if we or our partners cannot agree
    with the government or other third-party payers regarding the price we can charge for our medicines, we may not be able to sell our medicines in that market. Similarly, cost control initiatives by governments or third-party payers could decrease the
    price received for our medicines or increase patient coinsurance to a level that makes our medicines, including our commercial medicines and our medicines in development, economically unviable. If the pricing of any of our medicines decreases for any
    reason, it will reduce our revenue for such medicine. For example, Biogen has in the past disclosed that SPINRAZA revenue decreased in part due to lower pricing in the U.S. and certain rest-of-world markets.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The degree of market acceptance for our medicines, including our commercial medicines and our medicines in development, depends upon a
    number of factors, including the:</div>

  <div><br/>
  </div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">receipt and scope of marketing authorizations;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">establishment and demonstration in the medical and patient community of the efficacy and safety of our medicines, public perception regarding our medicines and their
            potential advantages over competing products;</div>
        </td>

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  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cost and effectiveness of our medicines compared to other available therapies;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">patient convenience of the dosing regimen for our medicines; and</div>
        </td>

  </tr>


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  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">reimbursement policies of government and third-party payers.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on the profile of our medicines, physicians, patients, patient advocates, payers or the medical community in general may not accept
    or use any of the medicines that we or our partners may develop.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, the product label for WAYLIVRA in the EU requires regular blood monitoring, which has negatively affected our ability to
    attract and retain patients for this medicine.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If government or other third-party payers fail to provide adequate coverage and payment rates for our medicines, including our commercial
    medicines and our medicines in development, our revenue will be limited.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In both domestic and foreign markets, sales of our current and future products will depend in part upon the availability of coverage and
    reimbursement from third-party payers. The majority of patients in the U.S. who would fit within our target patient populations for our medicines have their healthcare supported by a combination of Medicare coverage, other government health programs
    such as Medicaid, managed care providers, private health insurers and other organizations. Coverage decisions may depend upon clinical and economic standards that disfavor new medicines when more established or lower cost therapeutic alternatives are
    already available or subsequently become available. Assuming coverage is approved, the resulting reimbursement payment rates might not be enough to make our medicines affordable. Even if favorable coverage status and adequate reimbursement rates are
    attained, less favorable coverage policies and reimbursement rates may be implemented in the future. Accordingly, our commercial medicines and our medicines in development will face competition from other therapies and medicines for limited financial
    resources. Furthermore, we or our partners may need to conduct post-marketing studies to demonstrate the cost-effectiveness of any future products to satisfy third-party payers. These studies might require us to commit a significant amount of
    management time and financial and other resources. In addition, third-party payers may never consider our future products as cost-effective and adequate third-party coverage and reimbursement might not be available to enable us to maintain price levels
    sufficient to realize an appropriate return on investment in product development.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Third-party payers, whether foreign or domestic, or governmental or commercial, are developing increasingly sophisticated methods of
    controlling healthcare costs. In addition, in the U.S., no uniform policy of coverage and reimbursement for medicines exists among third-party payers. Therefore, coverage and reimbursement for medicines can differ significantly from payer to payer. For
    example, the Affordable Care Act, or ACA, was passed in March 2010, and substantially changed the way healthcare is financed by both governmental and private insurers and continues to significantly impact the U.S. pharmaceutical industry. There have
    been judicial and Congressional challenges to certain aspects of the ACA, as well as efforts to repeal or replace certain aspects of the ACA. It is unclear how future litigation and healthcare reform measures will impact the ACA and our business.</div>

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    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Further, we believe that future coverage, reimbursement and pricing will likely be subject to increased restrictions both in the U.S. and
    in international markets. In the U.S., recent health reform measures have resulted in reductions in Medicare and other healthcare funding, and there have been several recent U.S. Congressional inquiries, legislation and executive orders designed to,
    among other things, reduce drug prices, increase competition (including by enhancing support for generic and biosimilar drugs), lower out-of-pocket drug costs for patients, curtail spread pricing practices by pharmacy benefit managers, and foster
    scientific innovation to promote better health care and improved health. In addition, the Inflation Reduction Act of 2022, or the IRA, includes key actions aimed at reducing the costs of prescription drugs and allows HHS to negotiate the price of
    certain single-source drugs covered under Medicare and establish a price cap on such drugs. The IRA, among other things, (1) directs HHS to negotiate the price of certain single-source drugs and biologics that have been on the market for at least seven
    years covered under Medicare, or the Medicare Drug Price Negotiation Program, and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation. These provisions began to take effect progressively
    starting in fiscal year 2023, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges. Under this program, HHS has already announced the agreed-upon prices of the first drugs that were subject to price negotiations
    and will announce the agreed-upon prices of additional drugs in the coming years. In response to an October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center that will
    be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care. It is unclear whether the models will be utilized in any health reform measures in the future. Further, on December 7, 2023, the Biden
    administration announced an initiative to control the price of prescription drugs using march-in rights under the Bayh-Dole Act. On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance
    Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights. While march-in rights have not previously been exercised, it
    is uncertain if that will continue under the new framework. It is unclear whether or how these selected models or similar policy initiatives will impact prescription drug pricing in the future, particularly in light of the recent U.S. presidential and
    congressional elections.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payments from private
    payers. Our future product sales may be subject to additional discounts from list price in the form of rebates and discounts provided to covered entities under the Public Health Service Act 340B drug pricing program. Changes to the 340B program or to
    Medicare or Medicaid programs at the federal or state level, including outcomes of ongoing litigation in our industry, may impact our product prices and rebate liability.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and
    biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from
    other countries and bulk purchasing. For example, on January 5, 2024, the FDA approved Florida&#8217;s Section 804 Importation Program, or SIP, proposal to import certain drugs from Canada for specific state healthcare programs. It is unclear how this
    program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada. Other states have also submitted SIP proposals that are pending review by the FDA. Any such approved
    importation plans, when implemented, may result in lower drug prices for products covered by those programs. Third-party coverage and reimbursement for medicines may not be available or adequate in either the U.S. or international markets, which would
    negatively affect the potential commercial success of our products, our revenue and our profits.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we or our partners fail to compete effectively, our medicines, including our commercial medicines and our medicines in development,
    will not generate significant revenues.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our competitors engage in drug discovery throughout the world, are numerous, and include, among others, major pharmaceutical companies and
    specialized biopharmaceutical firms. In addition, other companies are engaged in developing RNA-targeted technology. Our competitors may succeed in developing medicines that are:</div>

  <div><br/>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">priced lower than our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">reimbursed more favorably by government and other third-party payers than our medicines;</div>
        </td>

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  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">safer than our medicines;</div>
        </td>

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</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">more effective than our medicines; or</div>
        </td>

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</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">more convenient to use than our medicines.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These competitive developments could make our medicines, including our commercial medicines and our medicines in development, obsolete or
    non-competitive.</div>

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    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certain of our partners are pursuing other technologies or developing other medicines either on their own or in collaboration with others,
    including our competitors, to treat some of the same diseases our own collaborative programs target. Competition may negatively impact a partner&#8217;s focus on and commitment to our medicines and, as a result, could delay or otherwise negatively affect the
    commercialization of our medicines, including our commercial medicines and our medicines in development.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Many of our competitors have substantially greater financial, technical and human resources than we do. In addition, many of these
    competitors have significantly greater experience than we do in conducting preclinical testing and human clinical studies of new pharmaceutical products, in obtaining FDA and other regulatory authorizations of such products and in commercializing such
    products. Accordingly, our competitors may succeed in obtaining regulatory authorization for products earlier than we do or more successfully commercialize their products.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are several pharmaceutical and biotechnology companies engaged in the development or commercialization in certain geographic markets
    of products against targets that are also targets of products in our development pipeline or of medicines we are commercializing. For example:</div>

  <div><br/>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Acoramidis, patisiran, tafamidis, tafamidis meglumine and vutrisiran compete with WAINUA;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Nexiguran ziclumeran, ALXN2220 and NNC6019-0001 could compete with WAINUA;</div>
        </td>

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</table>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Plozasiran, pegozafermin and NST-1024 could compete with TRYNGOLZA and WAYLIVRA;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Lanadelumab-flyo, C1 esterase inhibitor, berotralstat, C1 esterase inhibitor subcutaneous,
              garadacimab, </span>deucrictibant,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160; NTLA-2002 and STAR-0215 could compete with donidalorsen;</span></div>
        </td>

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</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Olpasiran, </span>zerlasiran, lepodisiran and muvalaplin <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">could compete with pelacarsen;</span></div>
        </td>

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</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NI-005/AP-101 could compete with QALSODY;</div>
        </td>

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</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">VIR-2218, VIR-3434, BRII-179, AB-729, selgantolimod,</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">bersacapavir,&#160; REP 2139-Mg and VTP-300 could complete with bepirovirsen;</span></div>
        </td>

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</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Budesonide, sparsentan, atrasentan, iptacopan, zigakibart, sibeprenlimab, atacicept, ravulizumab, vemircopan, felzartamab, telitacicept and povetacicept could compete
            with sefaxersen; and</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">GTX-102, alogabat and NNZ-2591 could compete with ION582.</div>
        </td>

  </tr>


</table>
  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA injection for intrathecal use is an antisense medicine indicated for the treatment of SMA patients of all ages approved in over
    50 countries. Specifically, SPINRAZA faces competition from onasemnogene abeparvovec, a gene therapy product that was approved in the U.S. in May 2019 and in the EU in May 2020 for the treatment of SMA, as well as risdiplam, an oral product for the
    treatment of SMA that was approved in the U.S. in August 2020 and in the EU in March 2021. Biogen has in the past disclosed that SPINRAZA revenue decreased due to a reduction in demand as a result of increased competition and that future sales of
    SPINRAZA may be adversely affected by competing products.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, companies that are developing medicines that
      target the same patient populations as our medicines in development may compete with us to enroll participants in the clinical trials for such medicines, which could make it more difficult for us to complete enrollment for these clinical trials</span>.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our medicines could be subject to regulatory limitations following approval.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Following approval of a medicine, we and our partners must comply with comprehensive government regulations regarding the manufacture,
    marketing and distribution of medicines. Promotional communications regarding prescription medicines must be consistent with the information in the product&#8217;s approved labeling. We or our partners may not obtain the labeling claims necessary or
    desirable to successfully commercialize our medicines, including our commercial medicines and our medicines in development.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA and foreign regulatory bodies have the authority to impose significant restrictions on an approved medicine through the product
    label and on advertising, promotional and distribution activities.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prescription medicines may be promoted only for the approved indication(s) in accordance with the approved label. The FDA and other
    regulatory authorities actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, when approved, the FDA or a foreign regulatory authority may condition approval on the performance of post-approval
    clinical studies or patient monitoring, which could be time consuming and expensive. For example, in connection with the conditional marketing approval for WAYLIVRA in the EU, we are required to conduct a post-authorization safety study to evaluate the
    safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. If the results of such post-marketing studies are not satisfactory, the FDA, EC or other foreign regulatory authorities may withdraw marketing authorization or may
    condition continued marketing on commitments from us or our partners that may be expensive and time consuming to fulfill.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we or others identify side effects after any of our medicines are on the market, or if manufacturing problems occur subsequent to
    regulatory approval, or if we, our CMOs or our partners fail to comply with regulatory requirements, we or our partners may, among other things, lose regulatory approval and be forced to withdraw products from the market, need to conduct additional
    clinical studies, incur restrictions on the marketing, distribution or manufacturing of the product, and/or change the labeling of our medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on our collaborations with Biogen for the development and commercialization of SPINRAZA and QALSODY.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have entered into separate collaborative arrangements with Biogen to develop and commercialize SPINRAZA and QALSODY. We entered into
    these collaborations primarily to:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">fund our development activities for SPINRAZA and QALSODY;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">seek and obtain regulatory approvals for SPINRAZA and QALSODY; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">successfully commercialize SPINRAZA and QALSODY.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are relying on Biogen to obtain additional regulatory approvals for SPINRAZA and QALSODY, generate additional clinical data for
    SPINRAZA and QALSODY, manufacture SPINRAZA and QALSODY, and successfully commercialize SPINRAZA and QALSODY. In general, we cannot control the amount and timing of resources that Biogen devotes to our collaborations. If Biogen fails to further develop
    SPINRAZA or QALSODY, obtain additional regulatory approvals for SPINRAZA or QALSODY, manufacture SPINRAZA or QALSODY, or successfully commercialize SPINRAZA or QALSODY, or if Biogen&#8217;s efforts in any of these respects are ineffective, revenues for
    SPINRAZA or QALSODY would be negatively affected.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, our collaborations with Biogen may not continue for various reasons. Biogen can terminate our collaborations at any time. If
    Biogen stops developing or commercializing SPINRAZA or QALSODY, we would have to seek or spend additional funding, and SPINRAZA&#8217;s or QALSODY&#8217;s commercialization may be harmed.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on our collaboration with AstraZeneca for the joint development and commercialization of WAINUA.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have entered into a collaborative arrangement with AstraZeneca to develop and commercialize WAINUA. Under the terms of the
    collaboration agreement, we and AstraZeneca will co-develop and co-commercialize WAINUA in the U.S. and AstraZeneca will have the sole right to commercialize WAINUA in all other countries. As a company we do not have experience with
    co-commercialization arrangements. We also do not have control over (1) the amount and timing of resources that AstraZeneca devotes to our collaboration, particularly outside of the U.S; (2) the pricing and reimbursement strategies for WAINUA; and (3)
    whether AstraZeneca elects to terminate the collaborative arrangement. If the co-commercialization arrangement for WAINUA is not successful for any reason, WAINUA may not meet our commercial objectives and our revenues for WAINUA may be limited.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, a Joint Steering Committee, or JSC, having equal membership from us and AstraZeneca, and various subcommittees oversee and
    coordinate the development, manufacturing, commercialization and other exploitation activities for WAINUA in the U.S. by mutual agreement. If any subcommittee cannot reach unanimous agreement on any matter within its respective scope of authority, such
    matter may be referred to the JSC for resolution. If the JSC cannot come to a mutual agreement on any particular matter, this could delay our ability to develop or commercialize WAINUA.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we are not successful in expanding our manufacturing capabilities or cannot manufacture our medicines or contract with a third party to
    manufacture our medicines at costs that allow us to charge competitive prices to buyers, we cannot market our products profitably.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">To successfully commercialize any of our medicines, we need
      to optimize and manage large-scale commercial manufacturing capabilities either on a standalone basis or through a third-party manufacturer. As our drug development and commercial pipeline increases and matures, we will have a greater need for
      clinical trial and commercial manufacturing capacity. We will also need to ensure that we have the manufacturing capabilities in place to support advances in our drug development activities, such as new chemistries. While</span> we believe <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">our current capabilities and those we obtain through third-party manufacturers support our manufacturing needs now, it will be important to expand our manufacturing infrastructure
      in the future, which will likely require substantial expenditures. If we are not successful in executing this expansion, it could limit our ability to meet our manufacturing requirements and commercial objectives in the future.</span></div>

  <div><br/>
  </div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, we have limited experience manufacturing pharmaceutical products of the chemical class represented by our medicines, called
    oligonucleotides, on a commercial scale for the systemic administration of a medicine. There are a small number of suppliers for certain capital equipment and raw materials that we use to manufacture our medicines, and some of these suppliers will need
    to increase their scale of production to meet our projected needs for commercial manufacturing. If a supplier chooses to devote more resources to other products, especially products with higher manufacturing capacity needs, that could impact such
    supplier&#8217;s capability to deliver our requirements timely. Further, we must continue to improve our manufacturing processes to allow us to reduce our drug costs. We or our partners may not be able to manufacture our medicines at a cost or in quantities
    necessary to make commercially successful products.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Manufacturers, including us, must adhere to the FDA&#8217;s cGMP regulations and similar regulations in foreign countries, which the applicable
    regulatory authorities enforce through facilities inspection programs. We, our partners and our contract manufacturers may not comply or maintain compliance with cGMP, or similar foreign regulations. Non-compliance could significantly delay or prevent
    receipt of marketing authorizations for our medicines, including authorizations for our commercial medicines and our medicines in development, or could result in enforcement action after authorization that might limit the commercial success of our
    medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We rely on third-party manufacturers to supply the drug substance and drug product for TRYNGOLZA and WAINUA and drug product for WAYLIVRA.
    The operations of our suppliers, many of which are located outside of the United States, are subject to additional risks that are beyond our control. For example, there have been Congressional legislative proposals, such as the recent bill titled the
    BIOSECURE Act, to discourage contracting with Chinese companies for the development or manufacturing of pharmaceutical products. In addition, merger and acquisition activity within the commercial manufacturing space could reduce the availability of
    resources from our third-party manufacturers. Delays or disruption to our own or third-party commercial manufacturing capabilities for any reason could limit the commercial success of our medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the Development and Regulatory Approval of our Medicines</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we or our partners fail to obtain regulatory approval for our medicines and additional approvals for our commercial medicines, we or
    our partners cannot sell them in the applicable markets.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We cannot guarantee that any of our medicines will be considered safe and effective or will be approved for commercialization. In
    addition, it is possible that our commercial medicines may not be approved in additional markets or for additional indications. We and our partners must conduct time-consuming, extensive and costly clinical studies to demonstrate the safety and
    efficacy of each of our medicines before they can be approved or receive additional approvals for sale. We and our partners must conduct these studies in compliance with FDA regulations and with comparable regulations in other countries.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partners may not obtain necessary regulatory approvals on a timely basis, if at all, for our medicines. It is possible that
    regulatory authorities will not approve our medicines for marketing or our commercial medicines in additional markets or for additional indications. If the FDA or another regulatory authority believes that we or our partners have not sufficiently
    demonstrated the safety or efficacy of any of our medicines, including our commercial medicines or our medicines in development, the authority will not approve the specific medicine or will require additional studies, which could be time consuming and
    expensive and delay or harm commercialization of the medicine. For example, in August 2018 we received a complete response letter from the FDA regarding the new drug application for WAYLIVRA in which the FDA determined that the safety concerns
    identified with WAYLIVRA in our clinical development program outweighed the expected benefits of triglyceride lowering in patients with FCS. We also received a Notice of Non-Compliance Withdrawal Letter, or Non-W, from Health Canada for WAYLIVRA in
    November 2018.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA or other comparable foreign regulatory authorities can delay, limit or deny approval of a medicine for many reasons, including:</div>

  <div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may disagree with the design or implementation of our clinical studies;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners may be unable to demonstrate to the satisfaction of the FDA or other regulatory authorities that a medicine is safe and effective for any indication;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may not accept clinical data from studies conducted at clinical facilities that have deficient clinical practices or that are in countries where the
            standard of care is potentially different from the U.S.;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners may be unable to demonstrate that our medicine&#8217;s clinical and other benefits outweigh its safety risks to support approval;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may disagree with the interpretation of data from preclinical or clinical studies;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may find deficiencies in the manufacturing processes or facilities of third-party manufacturers who manufacture clinical and commercial supplies for our
            medicines; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the approval policies or regulations of such authorities or their prior guidance to us or our partners during clinical development may significantly change in a manner
            rendering our clinical data insufficient for approval.</div>
        </td>

  </tr>


</table>
  <div><br/>
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    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Failure to receive marketing authorization for our medicines in development, or failure to receive additional marketing authorizations for
    our commercial medicines, or delays in these authorizations, could prevent or delay commercial introduction of the medicine, and, as a result, could negatively impact our ability to generate revenue from product sales.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the results of clinical testing indicate that any of our medicines are not suitable for commercial use, we may need to abandon one or
    more of our drug development programs.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug discovery and drug development have inherent risks and the historical failure rate for drugs is high. Antisense medicines are a
    relatively new approach to therapeutics. If we cannot demonstrate that our medicines are safe and effective for human use in the intended indication(s), we may need to abandon one or more of our drug development programs.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even if our medicines are successful in preclinical and human clinical studies, the medicines may not be successful in late-stage clinical
    studies. Similarly, topline, preliminary or interim data we release for any of our clinical studies may not be indicative of full or final results from such study.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Successful results in preclinical or initial human clinical studies, including the Phase 2 results for some of our medicines in
    development, may not predict the results of subsequent clinical studies. If any of our medicines in Phase 3 clinical studies do not show sufficient safety and efficacy in patients with the targeted indication, or if such studies are discontinued for
    any other reason, it could negatively impact our development and commercialization goals for these medicines and our stock price could decline. In addition, we may release topline, preliminary or interim data for any of our clinical studies.&#160; The
    interim, topline or preliminary results we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated.&#160; As a result, such
    data should be viewed with caution until the final data are available.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the past, we have invested in clinical studies of medicines that have not met the primary clinical endpoints in their Phase 3 studies
    or have been discontinued for other reasons. For example, in October 2021, Biogen reported that QALSODY did not meet the primary clinical endpoint in the Phase 3 VALOR study; however, trends favoring QALSODY were seen across multiple secondary and
    exploratory measures of disease activity and clinical function. In addition, in March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest Huntington&#8217;s disease based on the results of a
    pre-planned review of data from the Phase 3 study conducted by an unblinded Independent Data Monitoring Committee. Similar results could occur in clinical studies for our other medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are a number of factors that could cause a clinical study to fail or be delayed, including:</div>

  <div><br/>
  </div>

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    <td style="width: 36pt;"/>

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    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the clinical study may produce negative or inconclusive results;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">regulators may require that we hold, suspend or terminate clinical research for noncompliance with regulatory requirements;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we, our partners, the FDA or foreign regulatory authorities could suspend or terminate a clinical study due to adverse side effects of a medicine on subjects or lack of
            efficacy in the trial;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">enrollment in our clinical studies may be slower than we anticipate;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners, including our independent clinical investigators, contract research organizations and other third-party service providers on which we rely, may not
            identify, recruit or train suitable clinical investigators at a sufficient number of study sites or timely enroll a sufficient number of study subjects in the clinical study;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the institutional review board for a prospective site might withhold or delay its approval for the study;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">people who enroll in the clinical study may later drop out due to adverse events, a perception they are not benefiting from participating in the study, fatigue with the
            clinical study process or personal issues;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a clinical study site may deviate from the protocol for the study;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the cost of our clinical studies may be greater than we anticipate;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our partners may decide not to exercise any existing options to license and conduct additional clinical studies for our medicines; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the supply or quality of our medicines or other materials necessary to conduct our clinical studies may be insufficient, inadequate or delayed.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Further, the FDA or other regulatory authorities could request, among other things, additional information or commitments before we can
    start or continue a clinical study, protocol amendments, increased safety monitoring, additional product labeling information, and post-approval commitments. This happened in connection with the conditional marketing approval for WAYLIVRA in the EU, as
    the European Commission is requiring us to conduct a post-authorization safety study to evaluate the safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. In addition, under accelerated approval the FDA is requiring
    completion of the ongoing Phase 3 trial for QALSODY to confirm the clinical benefit of QALSODY.</div>

  <div><br/>
  </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Moreover, our commercial medicines are chemically similar to each other. As a result, a safety observation we encounter with one of our
    medicines could have, or be perceived by a regulatory authority to have, an impact on a different medicine we are developing. This could cause the FDA or other regulators to ask questions or take actions that could harm or delay our ability to develop
    and commercialize our medicines or increase our costs. Any failure or delay in our clinical studies could reduce the commercial potential or viability of our medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on third parties to conduct clinical studies for our medicines and any failure of those parties to fulfill their obligations
    could adversely affect our development and commercialization plans.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We depend on independent clinical investigators, contract research organizations and other third-party service providers to conduct our
    clinical studies for our medicines and expect to continue to do so in the future. For example, we use clinical research organizations, such as Icon Clinical Research Limited, Medpace, Inc., Parexel International Corporation, Syneos Health, Inc. and
    Thermo Fisher Scientific Inc. for the clinical studies for our medicines, including WAINUA for the treatment of ATTR-CM, donidalorsen, olezarsen, ulefnersen and zilganersen. We rely heavily on these parties for successful execution of our clinical
    studies, but do not control many aspects of their activities. For example, the investigators are not our employees, but we are responsible for ensuring that such investigators conduct each of our clinical studies in accordance with the general
    investigational plan and approved protocols for the study. Third parties may not complete activities on schedule or may not conduct our clinical studies in accordance with regulatory requirements or our stated protocols. For example, some of our key
    vendors have in the past experienced labor shortages, which impacted their ability to perform services for us for certain of our clinical trials. Subsequent failures of these third parties to carry out their obligations, or a termination of our
    relationship with such third parties, could delay or prevent the development, marketing authorization and commercialization of our medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, while we do not have any clinical trial sites in Russia, Ukraine or Gaza, we do have a limited number of clinical trial sites
    in Israel that may be materially impacted by the ongoing military conflicts in Israel and elsewhere in the Middle East and could result in difficulties enrolling or completing our clinical trials in such areas on schedule.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Since corporate partnering is part of our strategy to fund the advancement and commercialization of our development programs, if any of
    our collaborative partners fail to fund our collaborative programs, or if we cannot obtain additional partners, we may have to delay or stop progress on our drug development programs.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To date, corporate partnering has played a significant role in our strategy to fund our development programs and to add key development
    resources. While we are now commercializing some of our medicines independently, we still plan to continue to rely on additional collaborative arrangements to develop and commercialize some of our unpartnered medicines. However, we may not be able to
    negotiate favorable collaborative arrangements for these drug programs. If we cannot continue to secure additional collaborative partners, our revenues could decrease and the development of our medicines could suffer.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our corporate partners are developing and funding many of the medicines in our development pipeline. For example, we are relying on:</div>

  <div><br/>
  </div>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AstraZeneca for the joint development and funding of WAINUA;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis for development and funding of pelacarsen;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">GSK for development and funding of bepirovirsen; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Roche for development and funding of sefaxersen.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If any of these pharmaceutical companies stops developing and funding these medicines, our business could suffer and we may not have, or
    be willing to dedicate, the resources available to develop these medicines on our own. Our collaborators can terminate their relationships with us under certain circumstances, many of which are outside of our control. For example, in 2022, Pfizer and
    Bayer decided to discontinue the clinical development programs for vupanorsen and fesomersen, respectively.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even with funding from corporate partners, if our partners do not effectively perform their obligations under our agreements with them, it
    would delay or stop the progress of our drug development and commercial programs.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to receiving funding, we enter into collaborative arrangements with third parties to:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">conduct clinical studies;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">seek and obtain marketing authorizations; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">manufacture and commercialize our medicines.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Once we have secured a collaborative arrangement to further develop and commercialize one of our drug development programs, such as our
    collaborations with AstraZeneca, Biogen, GSK, Novartis, Otsuka and Roche, these collaborations may not continue or result in commercialized medicines, or may not progress as quickly as we anticipated.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, a collaborator such as AstraZeneca, Biogen, GSK, Novartis, Otsuka or Roche, could determine that it is in its financial
    interest to:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">pursue alternative technologies or develop alternative products that may be competitive with the medicine that is part of the collaboration with us;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">pursue higher-priority programs or change the focus of its own development programs; or</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">choose to devote fewer resources to our medicines than it does to its own medicines.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If any of these occur, it could affect our partner&#8217;s commitment to the collaboration with us and could delay or otherwise negatively
    affect the commercialization of our medicines, including QALSODY, SPINRAZA, WAINUA, bepirovirsen, donidalorsen, sefaxersen and pelacarsen.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We may not be able to benefit from designations for our medicines from regulatory authorities that are intended to confer benefits such as
    financial incentives or an accelerated regulatory pathway.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the U.S., under the Orphan Drug Act, the FDA may designate a medicine as an Orphan Drug if it is intended to treat a rare disease or
    condition affecting fewer than 200,000 individuals in the U.S. Orphan Drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process, but it can provide financial incentives, such as tax
    advantages and user-fee waivers, as well as longer regulatory exclusivity periods. The FDA has granted Orphan Drug designation to TRYNGOLZA for the treatment of patients with FCS, to WAINUA for the treatment of patients with ATTR, to ulefnersen for the
    treatment of patients with FUS-ALS, to ION582 for the treatment of patients with Angelman syndrome, and to some of our earlier stage medicines. The FDA and EMA have granted Orphan Drug designation to donidalorsen for the treatment of patients with HAE,
    to WAYLIVRA for the treatment of patients with FCS, to tominersen for the treatment of patients with HD, and to some of our earlier stage medicines. In addition, the EMA has granted Orphan Drug designation to WAYLIVRA for the treatment of patients with
    FPL. Even if approval is obtained on a medicine that has been designated as an Orphan Drug, we may lose Orphan Drug exclusivity if the FDA or EMA determines that the request for designation was materially defective or if we cannot assure sufficient
    quantity of the applicable medicine to meet the needs of patients with the rare disease or condition, or if a competitor is able to gain approval for the same or a substantially similar medicine in a safer or more effective form or that makes a major
    contribution to patient care. If we lose Orphan Drug exclusivity on any of our medicines, we may face increased competition and lose market share for such medicine.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a id="_Hlk189487623"><!--Anchor--></a>We may also seek rare pediatric disease designation for some of our medicines. The FDA defines
    &#8220;rare pediatric disease&#8221; as a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years or is a rare disease or condition within the meaning of the Orphan Drug
    Act. Designation of a medicine as a medicine for a rare pediatric disease does not guarantee that a marketing application for such medicine will meet the eligibility criteria for a rare pediatric disease priority review voucher, or PRV, at the time the
    application is approved. Under the FDCA, we will need to request a rare pediatric disease PRV in our original marketing application for any potential medicine for which we have received rare pediatric disease designation. The FDA may determine that a
    marketing application for any such medicine, if approved, does not meet the eligibility criteria for a PRV. Under the current statutory sunset provisions, after December 20, 2024, the FDA may only award a PRV for an approved rare pediatric disease
    application if the sponsor has rare pediatric disease designation for the drug or biologic that is the subject of such application, and that designation was granted by December 20, 2024. After September 30, 2026, the FDA may not award any rare
    pediatric disease PRVs. However, it is possible the authority for FDA to award rare pediatric disease PRV will be further extended by Congress.</div>

  <div><br/>
  </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Associated with our Businesses as a Whole</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our financial condition</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we fail to obtain timely funding, we may need to curtail or abandon some of our programs.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Many of our medicines are undergoing clinical studies or are in the early stages of research and development. Most of our programs will
    require significant additional research, development, manufacturing, preclinical and clinical testing, marketing authorizations, preclinical activities and commitment of significant additional resources prior to their successful commercialization. In
    addition, as we commercialize more medicines on our own, we will need to invest significant financial resources to continue developing the infrastructure required to successfully commercialize our medicines, including building and maintaining new
    support functions and scaling up existing internal support functions and expanding our manufacturing capabilities. All of these activities will require significant cash. As of December 31, 2024, we had cash, cash equivalents and short-term investments equal to $2.3 billion. If we or our partners do not meet our goals to successfully commercialize our medicines, including our commercial medicines, or to license certain medicines and proprietary technologies, we will need
    additional funding in the future. Our future capital requirements will depend on many factors such as:</div>

  <div><br/>
  </div>

  <div><a id="_Hlk188452784"><!--Anchor--></a></div>
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span></td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">successful commercialization of our commercial medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the profile and launch timing of our medicines in development;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">changes in existing collaborative relationships and our ability to establish and maintain additional collaborative arrangements;</div>
        </td>

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    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">continued scientific progress in our research, drug discovery and development programs;</div>
        </td>

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    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the size of our programs and progress with preclinical and clinical studies;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the time and costs involved in obtaining marketing authorizations;</div>
        </td>

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    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">competing technological and market developments, including the introduction by others of new therapies that address our markets; and</div>
        </td>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our manufacturing requirements and capacity to fulfill such requirements.</div>
        </td>

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</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we need additional funds, we may need to raise them through public or private financing. Additional financing may not be available on
    acceptable terms or at all. If we raise additional funds by issuing equity securities, the shares of existing stockholders will be diluted and the price, as well as the price of our other securities, may decline. For example, in September 2024, we
    completed an underwritten public offering of 11,500,000 shares of our common stock for total net proceeds, after deducting underwriting discounts and commissions and other offering expenses payable by us, of approximately $489.1 million. If adequate
    funds are not available or not available on acceptable terms, we may have to cut back on one or more of our research, drug discovery or development programs, or commercial operations. Alternatively, we may obtain funds through arrangements with
    collaborative partners or others, which could require us to give up rights to certain of our technologies or medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We have incurred losses, and our business will suffer if we fail to consistently achieve profitability in the future.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Because drug discovery and development require substantial lead-time and money prior to commercialization, our expenses have generally
    exceeded our revenue since we were founded in January 1989. As of December 31, 2024, we had an accumulated deficit of approximately $<ix:nonFraction name="us-gaap:RetainedEarningsAccumulatedDeficit" id="Fact_1bf4e795cb664f31987e0c971956d629" contextRef="c20241231" unitRef="U001" decimals="-8" scale="9" sign="-" format="ixt:num-dot-decimal">2.2</ix:nonFraction> billion and stockholders&#8217; equity of approximately $<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_b889069e95934021b877cb1e756b79b6" contextRef="c20241231" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">0.6</ix:nonFraction>
    billion. Most of our income has historically come from collaborative arrangements, including commercial revenue from royalties and R&amp;D revenue, with additional income from research grants and the sale or licensing of our patents, as well as
    interest income. We will now and continuing into the foreseeable future need to invest significant financial resources to commercialize medicines on our own and expect that our income in the future will be driven primarily by commercial sales. If we do
    not earn substantial revenue from commercial sales, we may incur additional operating losses in the future, which could restrict our ability to successfully develop additional medicines or sustain future profitability.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We may not be entitled to obtain additional milestone payments under our royalty monetization agreement with Royalty Pharma.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a Royalty Purchase Agreement with Royalty Pharma Investments. In addition to the $500 million we received
    at closing, this agreement makes available to us up to an additional $625 million in milestone payments. However, these additional milestone payments are subject to satisfaction of certain conditions related to the regulatory approval or commercial
    sales of pelacarsen, in certain cases by specific deadlines. Should we not satisfy such conditions by the applicable deadlines, or if we fail to meet our obligations or default under this agreement, the actual amount of additional payments to us could
    be substantially less than the maximum amounts available thereunder.</div>

  <div><br/>
  </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our intellectual property</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we cannot protect our patent rights or our other proprietary rights, others may compete more effectively against us.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our success depends to a significant degree upon whether we can continue to develop, secure and maintain intellectual property rights to
    proprietary products and services. However, we may not receive issued patents on any of our pending patent applications in the U.S. or in other countries and we may not be able to obtain, maintain or enforce our patents and other intellectual property
    rights, any of which could impact our ability to compete effectively. In addition, the scope of any of our issued patents may not be sufficiently broad to provide us with a competitive advantage. Furthermore, other parties may successfully challenge,
    invalidate or circumvent our issued patents or patents licensed to us so that our patent rights do not create an effective competitive barrier or revenue source.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We cannot be certain that the U.S. Patent and Trademark Office, or U.S. PTO, and courts in the U.S. or the patent offices and courts in
    foreign countries will consider the claims in our patents and applications covering our commercial medicines, or any of our medicines in development, as patentable. Method-of-use patents protect the use of a product for the specified method. This type
    of patent does not prevent a competitor from making and marketing a product that is identical to our product for an indication that is outside the scope of the patented method. Moreover, even if competitors do not actively promote their product for our
    targeted indications, physicians may prescribe these products off-label. Although off-label prescriptions may infringe or contribute to the infringement of method-of-use patents, the practice is common and such infringement is difficult to prevent,
    even through legal action.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we or any licensor partner loses or cannot obtain patent protection for our commercial medicines or any of our medicines in
    development, it could have a material adverse impact on our business.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intellectual property litigation could be expensive and prevent us from pursuing our programs.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we have to defend our intellectual property rights. If we are involved in an intellectual property dispute, we may need
    to litigate to defend our rights or assert them against others. Disputes can involve arbitration, litigation or proceedings declared by the U.S. PTO or the International Trade Commission or foreign patent authorities. Even if resolved in our favor,
    litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public
    announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If a third party claims that our medicines or technology infringe its patents or other intellectual property rights, we may have to
    discontinue an important product or product line, alter our products and processes, pay license fees or cease certain activities. We may not be able to obtain a license to needed intellectual property on favorable terms, if at all. There are many
    patents issued or applied for in the biotechnology industry, and we may not be aware of patents or patent applications held by others that relate to our business. This is especially true since patent applications in the U.S. are filed confidentially
    for the first 18 months. Moreover, the validity and breadth of biotechnology patents involve complex legal and factual questions for which important legal issues remain.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to product liability</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We are exposed to potential product liability claims, and insurance against these claims may not be available to us at a reasonable rate
    in the future or at all.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our business exposes us to potential product liability risks that are inherent in the testing, manufacturing, marketing and sale of
    therapeutic products, including potential product liability claims related to our commercial medicines and our medicines in development. We have clinical study insurance coverage and commercial product liability insurance coverage. However, this
    insurance coverage may not be adequate to cover claims against us, or be available to us at an acceptable cost, if at all. Regardless of their merit or eventual outcome, product liability claims may result in decreased demand for our medicines, injury
    to our reputation, withdrawal of clinical study volunteers and loss of revenues. Thus, whether or not we are insured, a product liability claim or product recall may result in losses that could be material.</div>

  <div><br/>
  </div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our personnel</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">The loss of key personnel, or the inability to attract and retain highly skilled personnel, could make it more difficult to run our
    business and reduce our likelihood of success.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are dependent on the principal members of our management,
      scientific and commercial staff. We do not have employment agreements with any of our employees that would prevent them from leaving us. The loss of our key management, scientific or commercial employees might slow the achievement of important
      research and development or commercial goals. It is also critical to our success that we recruit and retain qualified scientific personnel to perform research and development work and that we recruit and retain qualified marketing, sales, market
      access, distribution, and related personnel to commercialize our medicines. We may not be able to attract and retain skilled and experienced personnel on acceptable terms because of intense competition for experienced personnel among many
      pharmaceutical and health care companies, universities and non-profit research institutions. In addition, failure to succeed in clinical studies or in commercializing our medicines may make it more challenging to recruit and retain qualified
      personnel</span>.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to health epidemics, climate change and other events</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our business may be adversely affected by health epidemics, climate change, extreme weather events, fires, earthquakes, war, civil or
    political unrest, terrorism or other catastrophic events.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 40.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our business could be adversely affected by health epidemics in regions where we or our partners are commercializing our medicines, have
    concentrations of clinical trial sites or other business operations, and could cause disruption in the operations of third-party manufacturers and contract research organizations upon whom we rely. For example, enrollment in some of our clinical trials
    was delayed due to the COVID-19 pandemic.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In recent years, extreme weather events and changing weather patterns have become more common. As a result, we are potentially exposed to
    varying natural disaster or extreme weather risks such as fires, hurricanes, tornadoes, droughts, floods, or other events that may result from the impact of climate change on the environment, any of which could impact our business and manufacturing
    operations. The potential impacts of climate change may also include increased operating costs associated with additional regulatory requirements and investments in reducing energy, water use and greenhouse gas emissions. In addition, we currently
    manufacture most of our research and clinical supplies in a manufacturing facility located in Carlsbad, California, and various regions within California have recently experienced numerous catastrophic wildfires. We manufacture the finished drug
    product for TRYNGOLZA, WAYLIVRA and eplontersen for ongoing clinical trials at third-party contract manufacturers. Biogen manufactures the finished drug product for SPINRAZA and QALSODY and AstraZeneca is responsible for WAINUA&#8217;s commercial drug
    supply. The facilities and the equipment we, our partners and our contract manufacturers use to research, develop and manufacture our medicines would be costly to replace and could require substantial lead time to repair or replace.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our facilities or those of our partners or contract manufacturers may be harmed by natural disasters or other events outside our control,
    such as earthquakes, war, civil or political unrest, deliberate acts of sabotage, terrorism or industrial accidents such as fire and explosion, whether due to human or equipment error, and if such facilities are affected by a disaster or other event,
    our development and commercialization efforts would be delayed. Although we possess property damage and business interruption insurance coverage, this insurance may not be sufficient to cover all of our potential losses and may not continue to be
    available to us on acceptable terms, or at all. In addition, our development and commercialization activities could be harmed or delayed by a shutdown or significant disruption of the U.S. government, including the FDA or the U.S. PTO.</div>

  <div><br/>
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to personal information, cybersecurity, social media and artificial intelligence</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We are dependent on data as well as information technology systems and infrastructure, which exposes us to data protection risks.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are dependent upon our own and third-party data as well as information technology systems and infrastructure, including mobile
    technologies, to operate our business. The personal information we process subjects us to stringent and evolving U.S. and foreign laws, rules and regulations, contractual obligations, industry standards and other obligations related to data privacy and
    security. Our personal information obligations require us to implement and maintain certain practices, including those in relation to cross-border transfers of personal information. The multitude and complexity of our information technology systems and
    infrastructure make them vulnerable to a variety of evolving threats that may result in systems or data interruption, corruption, destruction, disruption of data integrity, malicious intrusion, or random attacks or other compromise (such as due to
    malfunctions, software vulnerabilities, natural disasters, telecommunications failures, malicious actors and personnel error). Data privacy or security incidents or breaches pose a risk that sensitive data, including our intellectual property, trade
    secrets or personal information of our employees, patients, customers or other business partners may be exposed to unauthorized persons. Cyber-attacks are increasing in their frequency, sophistication and intensity, particularly as companies (including
    us) continue to move to more remote work structures. In addition, the number and frequency of cybersecurity events globally may be heightened during times of geopolitical tension or instability between countries, including, for example, the ongoing war
    between Russia and Ukraine and military conflicts in the Middle East and the surrounding areas, or collectively, conflicts in Eastern Europe and the Middle East, as well as related political or economic responses and counter-responses by various global
    actors.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cybersecurity related events could include the deployment or use of harmful malware or malicious code, denial-of-service attacks,
    credential stuffing attacks, credential harvesting attacks, social engineering attacks (including deep fakes), ransomware and other means to affect the confidentiality, integrity or availability of our data as well as information systems and
    infrastructure. Our current, past and prospective business partners face similar risks and any security breaches of their systems could adversely affect our security posture. A security breach or privacy violation (including perceived breaches or
    violations) could result in any of the following, any of which could disrupt our business and result in increased costs or loss of revenue:</div>

  <div><br/>
  </div>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">harm our reputation;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">delay progress on the development of our medicines;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">compel us to comply with applicable security or data breach notification obligations (including laws);</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">result in the diversion of monetary funds and other company resources;</div>
        </td>

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</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">subject us to financial or other penalties, regulatory investigations or actions, including mandatory and costly corrective actions; and</div>
        </td>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">require us to verify the correctness of database contents and otherwise subject us to litigation or other liabilities.</div>
        </td>

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</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk mitigation strategies such as liability limitations in our contracts and insurance coverage may prove inadequate if there is a
    security breach or privacy violation. While we have invested, and continue to invest, in the protection of our data and information technology systems and infrastructure, our efforts may not be successful. Non-compliance with relevant data protection
    obligations or a failure to secure our data, information technology systems or infrastructure could adversely affect our business and operations and result in the loss of critical or sensitive information, which could result in financial, legal,
    business or reputational harm to us.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">The increasing use of social media platforms and artificial intelligence based software presents new risks and challenges.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Social media is increasingly being used to communicate about our medicines and the diseases our therapies are designed to treat. Social
    media practices in the biopharmaceutical industry continue to evolve and regulations relating to such use are not always clear and create uncertainty and risk of noncompliance with regulations applicable to our business. There is also a risk of
    inappropriate disclosure of sensitive information or negative or inaccurate posts or comments about us on social media. We may also encounter criticism on social media regarding our company, management, or medicines. Our reputation could be damaged by
    negative publicity or if adverse information concerning us is posted on social media platforms or similar mediums, which we may not be able to reverse. If any of these events were to occur or we otherwise fail to comply with applicable regulations, we
    could incur liability, face restrictive regulatory actions or incur other harm to our business.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, artificial intelligence, or AI, based software is increasingly being used in the biopharmaceutical industry. Use of AI based
    software may lead to the release of confidential proprietary information, which may impact our ability to realize the benefit of our intellectual property.</div>

  <div><br/>
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    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our securities and the global credit markets</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we do not progress in our programs as anticipated, the price of our securities could decrease.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For planning purposes, we estimate and may disclose the timing of a variety of clinical, regulatory and other milestones, such as when we
    anticipate a certain medicine will enter clinical trials, when we anticipate disclosing clinical data, when we anticipate completing a clinical study, or when we anticipate filing an application for, or obtaining, marketing authorization, or when we or
    our partners plan to commercially launch a medicine. We base our estimates on present facts and a variety of assumptions, many of which are outside of our control. If we do not achieve milestones in accordance with our or our investors&#8217; or securities
    analysts&#8217; expectations, including milestones related to our commercial medicines and medicines in development, the price of our securities could decrease. In addition, our share price may be dependent upon the valuations and recommendations of the
    analysts who cover our business. If our results do not meet these analysts&#8217; forecasts, the expectations of our investors or the financial guidance we provide to investors in any period, the market price of our common stock could decline. Our ability to
    meet analysts&#8217; forecasts, investors&#8217; expectations and our financial guidance is substantially dependent on our ability to maintain or increase sales of our commercial medicines, both partnered and unpartnered.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the price of our securities continues to be highly volatile, this could make it harder to liquidate your investment and could increase
    your risk of suffering a loss.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The market price of our common stock, like that of the
      securities of many other biopharmaceutical companies, has been and is likely to continue to be highly volatile. These fluctuations in our common stock price may significantly affect the trading price of our securities. During the 12 months preceding
    </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the closing market price of our common
      stock ranged from $</span>53.55<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to $</span>33.73<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> per share. Many factors can affect the market price of our securities,
      including, for example, fluctuations in our operating results, financing transactions, announcements of collaborations, clinical study results, technological innovations or new products being developed by us or our competitors, the commercial success
      of our approved medicines, governmental regulation, marketing authorizations, changes in payers&#8217; reimbursement policies, developments in patent or other proprietary rights and public concern regarding the safety of our medicines.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Broad market factors may materially harm the market price of our common stock irrespective of our operating performance. For example,
    events such as the ongoing conflicts in Eastern Europe and the Middle East have caused disruptions of global financial markets and resulted in increased volatility in the trading price of our common stock. In addition, industry factors may materially
    harm the market price of our common stock. Nasdaq, and the market for biotechnology companies in particular, have historically experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating
    performance of the particular companies affected. The trading prices and valuations of these stocks, and of ours, may not be predictable. A loss of investor confidence in the market for biotechnology or pharmaceutical stocks or the stocks of other
    companies that investors perceive to be similar to us, the opportunities in the biotechnology and pharmaceutical market or the stock market in general, could depress our stock price regardless of our business, prospects, financial conditions or results
    of operations.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Negative conditions in the global credit markets and financial services and other industries may adversely affect our business, financial
    condition or stock price.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The global credit and financial markets have experienced extreme volatility and disruptions recently, including as a result of the ongoing
    conflicts in Eastern Europe and the Middle East. These disruptions can result in severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about
    economic stability. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. If the current equity and credit markets deteriorate, it may make any necessary debt or
    equity financing more difficult, more costly and more dilutive. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our operations, growth plans, financial performance or stock
    price. In addition, our insurance carriers and insurance policies covering all aspects of our business may become financially unstable or may not be sufficient to cover any or all of our losses and may not continue to be available to us on acceptable
    terms, or at all.</div>

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    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">A variety of risks associated with operating our business and
      marketing our medicines internationally could adversely affect our business. In addition to our U.S. operations, we are commercializing WAYLIVRA in the EU, Latin America and certain Caribbean countries. We face risks associated with our international
      operations, including possible unfavorable regulatory, pricing and reimbursement, political, tax and labor conditions, which could harm our business. Because we have international operations, we are subject to numerous risks associated with
      international business activities, including</span>:</div>

  <div><br/>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">compliance with differing or unexpected regulatory requirements for our medicines and foreign employees;</div>
        </td>

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  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">complexities associated with managing multiple payer reimbursement regimes, government payers or patient self-pay systems;</div>
        </td>

  </tr>


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">difficulties in staffing and managing foreign operations;</div>
        </td>

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  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in certain circumstances, increased dependence on the commercialization efforts and regulatory compliance of third-party distributors or strategic partners;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">foreign government taxes, regulations and permit requirements;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">U.S. and foreign government tariffs, trade and export restrictions, price and exchange controls and other regulatory requirements;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">anti-corruption laws, including the Foreign Corrupt Practices Act, or the FCPA, and its equivalent in foreign jurisdictions;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">economic weakness, including inflation, natural disasters, war, acts of terrorism, political instability or public health issues or health epidemics, in particular
            foreign countries or globally;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">fluctuations in currency exchange rates, which could result in increased operating expenses and reduced revenue, and other obligations related to doing business in
            another country;</div>
        </td>

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  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the potential for a local seller, faced with higher local prices, importing medicines from an international market with lower prices rather than buying such medicines
            locally, which is referred to as parallel importation;</div>
        </td>

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  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">compliance with tax, employment, privacy, immigration and labor laws, regulations and restrictions for employees living or traveling abroad;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">workforce uncertainty in countries where labor unrest is more common than in the U.S.; and</div>
        </td>

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  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">changes in diplomatic and trade relationships.</div>
        </td>

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</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our business activities outside of the U.S. are subject to the FCPA and similar anti-bribery or anti-corruption laws, regulations or rules
    of other countries in which we operate, including the United Kingdom&#8217;s Bribery Act 2010. In many other countries, the healthcare providers who prescribe pharmaceuticals are employed by their government, and the purchasers of pharmaceuticals are
    government entities; therefore, any dealings with these prescribers and purchasers may be subject to regulation under the FCPA. There is no certainty that all employees and third-party business partners (including our contract research organizations,
    contract manufacturing organizations, distributors, wholesalers, agents, contractors and other partners) will comply with anti-bribery laws. Importantly, we do not control the actions of manufacturers and other third-party agents, although we may be
    liable for their actions. Violation of these laws may result in civil or criminal sanctions, which could include monetary fines, criminal penalties, and disgorgement of past profits, which could have an adverse impact on our business and financial
    condition.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Provisions in our certificate of incorporation, bylaws, convertible notes documents, call spread hedge transaction documents and Delaware
    law may prevent stockholders from receiving a premium for their shares.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our certificate of incorporation provides for classified terms for the members of our board of directors. Our certificate also includes a
    provision that requires at least 66 2/3 percent of our voting stockholders to approve a merger or certain other business transactions with, or proposed by, any holder of 15 percent or more of our voting stock, except in cases where certain directors
    approve the transaction or certain minimum price criteria and other procedural requirements are met.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our certificate of incorporation also requires that any action required or permitted to be taken by our stockholders must be taken at a
    duly called annual or special meeting of stockholders and may not be taken by written consent. In addition, only our board of directors, chairperson of the board or chief executive officer can call special meetings of our stockholders. We have in the
    past, and may in the future, implement a stockholders&#8217; rights plan, also called a poison pill, which could make it uneconomical for a third party to acquire our company on a hostile basis. In addition, our board of directors has the authority to fix
    the rights and preferences of, and issue shares of preferred stock, which may have the effect of delaying or preventing a change in control of our company without action by our stockholders.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The provisions of our convertible senior notes could make it more difficult or more expensive for a third party to acquire us. Upon the
    occurrence of certain transactions constituting a fundamental change, holders of the notes will have the right, at their option, to require us to repurchase all of their notes or a portion of their notes, which may discourage certain types of
    transactions in which our stockholders might otherwise receive a premium for their shares over the then-current market prices.</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2023, we completed a $575 million offering of 1.75% Notes and used $488.2 million of the net proceeds from the issuance of the 1.75%
    Notes to repurchase $504.4 million of our 0.125% Notes. In 2021, we completed a $632.5 million offering of 0% Notes and used $319.0 million of the net proceeds from the issuance of the 0% Notes to repurchase the remaining $309.9 million of our 1%
    Notes. In 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of our existing 1% Notes to exchange $375.6 million of our 1% Notes for $439.3 million of our 0.125% Notes, and
    to issue $109.5 million of our 0.125% Notes. Additionally, in connection with the pricing of our 0% Notes and 0.125% Notes, we entered into call spread transactions in which we purchased note hedges and sold warrants. For our 0.125% Notes, the note
    hedges expired upon maturity of the 0.125% Notes and the warrants will expire in March 2025. Terminating or unwinding the call spread transactions for our 0% Notes could require us to make substantial payments to the counterparties under those
    agreements or may increase our stock price. The costs or any increase in stock price that may arise from terminating or unwinding such agreements could make an acquisition of our company significantly more expensive to the purchaser.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These provisions, as well as Delaware law, including Section 203 of the Delaware General Corporation Law, and other of our agreements, may
    discourage certain types of transactions in which our stockholders might otherwise receive a premium for their shares over then-current market prices, and may limit the ability of our stockholders to approve transactions that they think may be in their
    best interests.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Future sales of our common stock in the public market could adversely affect the trading price of our securities.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Future sales of substantial amounts of our common stock in
      the public market, or the perception that such sales could occur, could adversely affect trading prices of our securities. For example, we may issue approximately 21.6 million shares of our common stock upon conversion of our 1.75% Notes and 0%
      Notes. In connection with the issuance of the 0% Notes, we entered into certain call spread transactions covering 10.9 million shares </span>that we expect will <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">offset the
      dilution to holders of common stock upon any conversion </span>of those notes. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">However, the anti-dilutive effect of the convertible note hedges is offset by certain
      warrant transactions we entered into in connection with the issuance of the 0% Notes. The addition of any of these shares into the public market may have an adverse effect on the price of our securities.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, pursuant to the call spread transactions we entered into in connection with the pricing of our 0% Notes, the counterparties
    are likely to modify their hedge positions from time to time at or prior to the conversion or maturity of the notes by purchasing and selling shares of our common stock, other of our securities, or other instruments, including over-the-counter
    derivative instruments, that they may wish to use in connection with such hedging, which may have a negative effect on the conversion value of those notes and an adverse impact on the trading price of our common stock. The call spread transactions are
    expected generally to reduce potential dilution to holders of our common stock upon any conversion of our 0% Notes or offset any cash payments we are required to make in excess of the principal amount of the converted 0% Notes, as the case may be.
    However, the warrant transactions could separately have a dilutive effect to the extent that the market value per share of our common stock exceeds the applicable strike price of the warrants.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to compliance with laws</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our operations are subject to extensive legal and regulatory requirements affecting the health care industry.</div>

  <div><br/>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operations are subject to extensive legal and regulatory requirements affecting the health care industry, including federal and state
    anti-kickback laws, false claims laws, transparency laws, such as the federal Sunshine Act, and health information privacy and security laws, which are subject to change at any time. It is possible that governmental authorities will conclude that our
    business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. Penalties for violations of applicable healthcare laws and regulations may include
    significant civil, criminal and administrative penalties, damages, disgorgement, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and additional reporting requirements and oversight
    if we enter into a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws. In addition, violations may also result in reputational harm, diminished profits and future earnings.</div>

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    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Because we use biological materials, hazardous materials, chemicals and radioactive compounds, if we do not comply with laws regulating
    the protection of the environment and health and human safety, our business could be adversely affected.</div>

  <div><br/>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and manufacturing activities involve the use of potentially harmful biological materials as well as materials,
    chemicals and various radioactive compounds that could be hazardous to human health and safety or the environment. We store most of these materials and various wastes resulting from their use at our facilities in Carlsbad, California pending ultimate
    use and disposal. We cannot completely eliminate the risk of contamination, which could cause:</div>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">interruption of our research, development and manufacturing efforts;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">injury to our employees and others;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">environmental damage resulting in costly clean up; and</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">liabilities under federal, state and local laws and regulations governing health and human safety, as well as the use, storage, handling and disposal of these materials
            and resultant waste products.</div>
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  <div><br/>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In such an event, we may be held liable for any resulting damages, and any liability could exceed our resources. Although we carry
    insurance for pollution liability in amounts and types that we consider commercially reasonable, the coverage or coverage limits of our insurance policies may not be adequate. If our losses exceed our insurance coverage, our financial condition would
    be adversely affected.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our business is subject to changing regulations for corporate governance and public disclosure that has increased both our costs and the
    risk of noncompliance.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Each year we are required to evaluate our internal control systems to allow management to report on, and our Independent Registered Public
    Accounting Firm to attest to, our internal controls as required by Section 404 of the Sarbanes-Oxley Act. As a result, we continue to incur additional expenses and divert our management&#8217;s time to comply with these regulations. In addition, if we cannot
    continue to comply with the requirements of Section 404 in a timely manner, we might be subject to sanctions or investigation by regulatory authorities, such as the SEC, the Public Company Accounting Oversight Board, or PCAOB, or The Nasdaq Global
    Select Market. Any such action could adversely affect our financial results and the market price of our common stock.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The SEC and other regulators have continued to adopt new rules and regulations and make additional changes to existing regulations that
    require our compliance. In July 2010, the Dodd-Frank Wall Street Reform and Protection Act, or the Dodd-Frank Act, was enacted, and in August 2022, the SEC adopted additional rules and regulations under the Dodd-Frank Act related to &#8220;say on pay&#8221; and
    proxy access. Stockholder activism, the current political environment and the current high level of government intervention and regulatory reform may lead to substantial new regulations and disclosure obligations, which has and may in the future lead
    to additional compliance costs and impact the manner in which we operate our business.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to taxes</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="_Hlk189489381"><!--Anchor--></a>Our ability to use our net operating loss carryovers and certain other tax attributes may be
    limited.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the Internal Revenue Code of 1986, as amended, or the Code, a corporation is generally allowed a deduction for net operating losses,
    or NOLs, carried over from a prior taxable year. Under the Code, we can carry forward our NOLs to offset our future taxable income, if any, until such NOLs are used or expire. The same is true of other unused tax attributes, such as tax credits.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the current U.S. federal income tax law, U.S. federal NOLs generated in taxable years beginning after December 31, 2017 may be
    carried forward indefinitely, but the deductibility of such U.S. federal NOLs is limited to 80 percent of taxable income.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, under Sections 382 and 383 of the Code, and corresponding provisions of state law, if a corporation undergoes an &#8220;ownership
    change,&#8221; which is generally defined as a greater than 50 percentage-point cumulative change, by value, in its equity ownership over a three-year period, the corporation&#8217;s ability to use its pre-change NOL carryforwards and other pre-change tax
    attributes to offset its post-change income or taxes may be limited. We may experience ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control. If an ownership change occurs
    and our ability to use our NOL carryforwards or other tax attributes is materially limited, it would harm our future operating results by effectively increasing our future tax obligations. As a result of our merger with Akcea Therapeutics, Inc. in
    2020, or the Akcea Merger, we are subject to the separate return limitation year, or SRLY, rules. Under the SRLY rules, our utilization of Akcea&#8217;s pre-merger NOL and tax credit carryforwards is limited to the amount of income that Akcea contributes to
    our consolidated taxable income. The Akcea pre-merger tax attributes cannot be used to offset any of the income that Ionis contributes to our consolidated taxable income. In addition, at the state level, there may be periods during which the use of
    NOLs is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed. For example, in June 2024, California enacted Senate Bill 167, or SB 167, which, with certain exceptions, suspends the ability to use California
    net operating losses to offset California income and limits the ability to use California business tax credits to offset California taxes, for taxable years beginning after 2023 and before 2027.</div>

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    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our future taxable income could be impacted by changes in tax laws, regulations and treaties.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A change in tax laws, treaties or regulations, or their interpretation, of any country in which we operate could materially affect us.</div>

  <div><br/>
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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We could be subject to additional tax liabilities.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are subject to U.S. federal, state, local and foreign
      income taxes, sales taxes in the U.S., withholding taxes and transaction taxes in foreign jurisdictions. Significant judgment is required in evaluating our tax positions and our worldwide provision for taxes. During the ordinary course of business,
      there are many activities and transactions for which the ultimate tax determination is uncertain. In addition, our tax obligations and effective tax rates could be adversely affected by changes in the relevant tax, accounting and other laws,
      regulations, principles and interpretations, including those relating to income tax nexus, by recognizing tax losses or lower than anticipated earnings in jurisdictions where we have lower statutory rates and higher than anticipated earnings in
      jurisdictions where we have higher statutory rates, by changes in foreign currency exchange rates, or by changes in the valuation of our deferred tax assets and liabilities. </span>In particular, our tax obligations and effective tax rate in the
    jurisdictions in which we conduct business could increase in the future as a result of the base erosion and profit shifting, or BEPS,&#160; project led by the Organization for Economic Co-operation and Development, or OECD, and other initiatives led by the
    OECD or the European Commission. The OECD is leading work on an iteration of the BEPS project based on two &#8220;pillars&#8221; (subject to certain revenue thresholds), involving the reallocation of taxing rights in respect of certain multinational enterprises
    above a fixed profit margin to the jurisdictions in which they carry on business) (referred to as &#8220;Pillar One&#8221;) and imposing a minimum effective corporate tax rate on certain multinational enterprises (referred to as &#8220;Pillar Two&#8221;). Based on the minimum
    revenue thresholds we do not expect to fall within the scope of these requirements in the near term.</div>

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  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We may be audited in various jurisdictions, and such
      jurisdictions may assess additional income, sales and value-added or other taxes against us. Although we believe our tax estimates are reasonable, the final determination of any tax audits or litigation could be materially different from our
      historical tax provisions and accruals, which could have a material adverse effect on our operating results or cash flows in the period for which a determination is made</span>.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item1B"><!--Anchor--></a>Item 1B. Unresolved Staff Comments</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item1C"><!--Anchor--></a>Item 1C. Cybersecurity</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have implemented and maintain various information security processes designed to detect, respond to, recover, and protect our
    technology ecosystem from cybersecurity threats. These processes are designed to identify, assess, and manage material risks that may result from cybersecurity threats and apply to our critical technologies inclusive of networks, third party hosted
    services, communications systems, hardware, software, and critical data, including intellectual property and confidential information that is proprietary, strategic, or competitive in nature.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our Information Technology department, led by our Senior Vice President, Information Technology, helps to detect, respond to, and manage
    cybersecurity threats and risks by monitoring and evaluating our threat environment using various manual and automated tools in certain environments and systems and other methods including, for example:</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">analyzing reports of certain threats and actors;</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">conducting scans of the threat environment;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">evaluating our and our industry&#8217;s risk profile;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">evaluating certain threats reported to us;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">conducting internal and external audits;</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">conducting threat assessments for certain internal and external threats; and</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">conducting vulnerability assessments designed to identify vulnerabilities.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Depending on the environment, system and data, we have implemented and maintain various technical, physical, and organizational measures,
    processes, standards, and policies designed to manage and mitigate material risks from cybersecurity threats to our critical technologies and data, including, for example:</div>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">incident response plan;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">disaster recovery/business continuity plans;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">risk assessments;</div>
        </td>

  </tr>


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">encryption of certain data;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">network security and access controls for certain systems;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">physical security;</div>
        </td>

  </tr>


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">asset management, tracking and disposal;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">systems monitoring; and</div>
        </td>

  </tr>


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">employee training.</div>
        </td>

  </tr>


</table>
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<div><br/>
  </div>
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  <ix:continuation id="Text_f3c0c420a3dc4633b17a369b6d9ec65f26" continuedAt="Text_f3c0c420a3dc4633b17a369b6d9ec65f27"><ix:nonNumeric name="cyd:CybersecurityRiskManagementProcessesIntegratedTextBlock" id="Text_5efe4db3c20843e395c0fa8952b0ae0a" contextRef="c20240101to20241231" escape="true">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our assessment and management of material risks from cybersecurity threats are <ix:nonNumeric name="cyd:CybersecurityRiskManagementProcessesIntegratedFlag" id="Fact_720bb66dfe2a4978bdce69575ca9ccc1" contextRef="c20240101to20241231" format="ixt:fixed-true">integrated into the Company&#8217;s overall risk management processes</ix:nonNumeric>. For example, cybersecurity risk is assessed as a component of our enterprise risk
    management program. In addition, we have developed a process whereby our senior management evaluates material risks from cybersecurity threats against our overall business objectives and reports certain cybersecurity incidents to the Audit Committee of
    the Board of Directors, which evaluates our overall enterprise risk. </div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use third-party providers to perform various functions throughout our business, such as application providers and hosting companies. <ix:nonNumeric name="cyd:CybersecurityRiskManagementThirdPartyEngagedFlag" id="Fact_bbfb9099cedc4131b08fd587faa28ce5" contextRef="c20240101to20241231" format="ixt:fixed-true">We use third-party providers to assist us from time to time in an effort to identify, assess, and manage material risks from cybersecurity threats, including, for example, legal counsel, cybersecurity consultants, cybersecurity software providers, penetration testing firms, and forensic investigators.</ix:nonNumeric>&#160;<ix:nonNumeric name="cyd:CybersecurityRiskThirdPartyOversightAndIdentificationProcessesFlag" id="Fact_0b39ee40156246639722dcaef9c1f9ac" contextRef="c20240101to20241231" format="ixt:fixed-true">The Company maintains a risk-based approach and process designed to identify and oversee cybersecurity risks presented by third parties, including vendors, service providers and other external users of the Company&#8217;s systems, as well as the systems of third parties that could materially impact our business if there is a cybersecurity incident affecting those third-party systems.</ix:nonNumeric></div>
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<div><br/>
  </div>
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  <ix:nonNumeric name="cyd:CybersecurityRiskMateriallyAffectedOrReasonablyLikelyToMateriallyAffectRegistrantTextBlock" id="Text_c8267c81acb7417789526926c9476737" contextRef="c20240101to20241231" escape="true"><ix:continuation id="Text_f3c0c420a3dc4633b17a369b6d9ec65f30">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For an additional description of the risks from cybersecurity
    threats that may materially <ix:nonNumeric name="cyd:CybersecurityRiskMateriallyAffectedOrReasonablyLikelyToMateriallyAffectRegistrantFlag" id="Fact_26adc3718a8a438fbd5114701617e11e" contextRef="c20240101to20241231" format="ixt:fixed-false">affect</ix:nonNumeric> us and how they may do so, see our risk factors under Item 1A, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk Factors</span>, in this Annual Report on Form 10-K, including the risk factor titled &#8220;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">We are
      dependent on data as well as information technology systems and infrastructure, which exposes us to data protection risks</span>.&#8221;</div>
</ix:continuation></ix:nonNumeric></div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Governance</div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="cyd:CybersecurityRiskBoardOfDirectorsOversightTextBlock" id="Text_21140e2f43b44cd69f77d721c56cff68" contextRef="c20240101to20241231" escape="true" continuedAt="Text_c7d7870312484ed38400f9b2f579ca1e1">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our Board of Directors addresses our cybersecurity risk management as part of its general oversight function. <ix:nonNumeric name="cyd:CybersecurityRiskBoardCommitteeOrSubcommitteeResponsibleForOversightTextBlock" id="Text_f8319135aa8a429e933a787dc7dd72f3" contextRef="c20240101to20241231" escape="true"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">The Audit Committee of the Board of Directors is responsible for overseeing our cybersecurity risk management processes, including oversight and mitigation of risks from cybersecurity threats.</span></ix:nonNumeric> The Audit Committee also oversees our internal audit department and management&#8217;s internal controls over financial reporting, including with respect to cybersecurity.</div>
</ix:nonNumeric>

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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_c7d7870312484ed38400f9b2f579ca1e2" continuedAt="Text_c7d7870312484ed38400f9b2f579ca1e3"><ix:nonNumeric name="cyd:CybersecurityRiskManagementPositionsOrCommitteesResponsibleTextBlock" id="Text_71ac86635d994c3dbba75d06f171758b" contextRef="c20240101to20241231" escape="true">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="cyd:CybersecurityRiskManagementPositionsOrCommitteesResponsibleFlag" id="Fact_86b466fc816b429ba53e991ce82bffe4" contextRef="c20240101to20241231" format="ixt:fixed-true">Our cybersecurity risk assessment and management processes are implemented and maintained by our Senior Vice President, Information Technology</ix:nonNumeric>, <ix:nonNumeric name="cyd:CybersecurityRiskManagementExpertiseOfManagementResponsibleTextBlock" id="Text_e24afed4a4684b40ab83c8aedc25c726" contextRef="c20240101to20241231" escape="true"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">who holds an undergraduate
    degree in Computer Engineering and has served in information technology and security roles dedicated to the pharmaceutical and biotechnology sector for approximately 18 years, including serving as the Chief Information Officer of two public
    biopharmaceutical companies.</span></ix:nonNumeric></div>
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<div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our Senior Vice President, Information Technology is
    responsible for hiring appropriate personnel, helping to integrate cybersecurity risk considerations into our overall risk management strategy, communicating key priorities to relevant personnel, helping prepare for cybersecurity incidents, approving
    cybersecurity processes, and reviewing security assessments and other security-related reports.</div>
</ix:nonNumeric></ix:nonNumeric></ix:continuation>
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  </div>
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  <ix:nonNumeric name="cyd:CybersecurityRiskProcessForInformingBoardCommitteeOrSubcommitteeResponsibleForOversightTextBlock" id="Text_e7509f0985564bdfac74bea5e869febd" contextRef="c20240101to20241231" escape="true"><ix:continuation id="Text_c7d7870312484ed38400f9b2f579ca1e6">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cybersecurity incident response plan is designed to
    escalate certain cybersecurity incidents, depending on the circumstances, to our senior management team and Audit Committee of the Board of Directors. <ix:nonNumeric name="cyd:CybersecurityRiskManagementPositionsOrCommitteesResponsibleReportToBoardFlag" id="Fact_76e38d813a9d4cb2be62dc517a9a26a0" contextRef="c20240101to20241231" format="ixt:fixed-true">The Audit Committee of the Board of Directors receives reports from our Senior Vice President, Information Technology</ix:nonNumeric> concerning our significant cybersecurity threats and risks (including certain cybersecurity threats) and the processes we
    have implemented that are designed to address them. </div>
</ix:continuation></ix:nonNumeric></div>

  <div><br/>
  </div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58</div>

    </div>

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      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item2"><!--Anchor--></a>Item 2. Properties</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of February 13, 2025, the
    following are the primary facilities in which we operate:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property Description</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; white-space: nowrap;">&#160;</td>

    <td style="width: 12.86%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Location</div>
        </td>

    <td style="width: 1.87%; vertical-align: top; white-space: nowrap;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Square</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Footage</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; white-space: nowrap;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">or Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; white-space: nowrap;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Initial Lease</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Term End Date</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; white-space: nowrap;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Lease</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Extension Options</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Laboratory and office space facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.86%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 1.87%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">176,300</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2037</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Two, five-year options to extend</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Office and meeting space facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.86%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 1.87%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,000</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2037</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Two, five-year options to extend</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Manufacturing facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.86%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 1.87%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,800</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Owned</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Manufacturing support facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.86%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 1.87%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,800</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">One, five-year option to extend</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Office space facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.86%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Boston, MA</div>
        </td>

    <td style="width: 1.87%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,300</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2029</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">One, five-year option to extend</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Office space facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.86%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 1.87%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,800</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">None</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Warehouse facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.86%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 1.87%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,200</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2028</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">None</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Office space facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.86%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dublin, Ireland</div>
        </td>

    <td style="width: 1.87%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; border-bottom: #000000 2px solid; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,900</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">None</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.86%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 1.87%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; border-top: #000000 2px solid; border-bottom: #000000 4px double; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">331,100</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that our current and future facilities will be adequate for the foreseeable future. Refer to Part IV, Section 15, Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated
      Financial Statements</span> for details on real estate transactions.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item3"><!--Anchor--></a>Item 3. Legal Proceedings</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For details of legal proceedings, refer to Part IV, Item 15, Note 11, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Legal Proceedings,</span> in the Notes to the Consolidated Financial Statements.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item4"><!--Anchor--></a>Item 4. Mine Safety Disclosures</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="PARTII"><!--Anchor--></a>PART II</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a id="Item5"><!--Anchor--></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Item 5. Market for Registrant</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Market Information and Dividends</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our common stock is traded publicly through The Nasdaq Global Select Market under the symbol &#8220;IONS.&#8221; As of February 13, 2025, there were approximately 447 stockholders of record of our common stock. Because many of our shares are held by brokers and other
    institutions on behalf of stockholders, we are unable to estimate the total number of stockholders represented by these record holders.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have never paid dividends and do not anticipate paying any dividends in the foreseeable future.</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Performance Graph (1)</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Set forth below is a table and chart comparing the total return on an indexed basis of $100 invested on December 31, 2019 in our common
    stock, the Nasdaq Composite Index (total return) and the Nasdaq Biotechnology Index. The total return assumes reinvestment of dividends.</div>

  <div><br/>
  </div>

  <div style="text-align: center;"><img width="707" height="587" src="image02.jpg" alt="graphic" style="height: 587px; width: 707px;"/></div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*&#160; $100 invested on December 31, 2019 in stock or index, including reinvestment of dividends. Fiscal year ending December 31.</div>

  <div><br/>
  </div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">COMPARISON OF 5 YEAR CUMULATIVE TOTAL RETURN</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Among Ionis Pharmaceuticals, Inc., the Nasdaq Composite Index,</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">and the Nasdaq Biotechnology Index</div>

  <div style="text-align: center;"><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-19</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-20</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-21</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-22</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-23</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-24</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis Pharmaceuticals, Inc.</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100.00</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">93.59</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.37</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62.52</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83.74</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.87</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Nasdaq Composite Index</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100.00</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">144.92</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">177.06</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">119.45</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">172.77</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">223.87</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Nasdaq Biotechnology Index</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100.00</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">126.42</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">126.45</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">113.65</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">118.87</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">118.20</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">___________</div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">This section is not &#8220;soliciting material,&#8221; is not deemed &#8220;filed&#8221; with the SEC, is not subject to the liabilities of Section 18 of the Exchange Act and is not to be
            incorporated by reference in any of our filings under the Securities Act or the Exchange Act, whether made before or after the date hereof and irrespective of any general incorporation language in any such filing.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 6<a id="Item6"><!--Anchor--></a>. Reserved</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a id="Item7"><!--Anchor--></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Item 7. Management</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s Discussion and Analysis of Financial Condition and Results of Operations</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">This financial review presents our operating results for each of the two years in the period ended December 31, 2024, and our financial condition as of December 31, 2024.
    Refer to Part II, Item 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations</span>, in our 2023 Form 10-K for our results of operations for 2023
    compared to 2022. Except for the historical information contained herein, the following discussion contains forward-looking statements that
    are subject to known and unknown risks, uncertainties and other factors that may cause our actual results to differ materially from those expressed or implied by such forward-looking statements. We discuss such risks, uncertainties and other factors
    throughout this report and specifically under Part I, Item 1A, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk Factors</span>. In addition, the following review should be read in conjunction with
    the information presented in our consolidated financial statements and the related notes to our consolidated financial statements included in Part II, Item 8, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Financial Statements and Supplementary Data</span>, of this report.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Overview</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As noted in our Business Overview in Part I, Item 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Business</span>, for three decades, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">we have invented medicines that we believe bring better futures to people with serious diseases. Today, as a
      pioneer in RNA-targeted medicines, we continue to drive innovation in RNA therapies.</span> We currently have six marketed medicines: TRYNGOLZA, WAINUA, SPINRAZA, QALSODY, TEGSEDI and WAYLIVRA. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We also have a rich innovative late- and mid-stage pipeline in neurology, cardiology and rare diseases. We currently have nine medicines in Phase 3 development and additional medicines in early and mid-stage development</span>.
    Refer to Part I, Item 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Business</span>, for further details on our business and key developments in our medicines.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Results of Operations</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Below we have included our results of operations for 2024 compared to 2023. Refer to Part II, Item 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations,</span> of our 2023
    Form 10-K for our results of operations for 2023 compared to 2022. The following table provides selected summary information from our consolidated statements of operations for 2024
    and 2023 (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">705.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">787.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,180.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,141.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss from operations</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(475.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(353.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(453.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(366.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash, cash equivalents and short-term investments</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,297.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,331.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue for 2024 was $705.1 million compared to $787.6 million in 2023 and was comprised of the following (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">216.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">240.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other commercial revenue:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA revenue, net</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total other commercial revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">308.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization from upfront payments</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">131.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">125.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">106.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">License fees</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">116.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other services</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.0</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">332.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">352.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA joint development revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">126.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">412.0</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">479.0</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: left; margin-left: 99pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">705.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">787.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue in 2024 included new sources of commercial revenue with the launch of WAINUA in the U.S. in late January 2024 and the
    launch of TRYNGOLZA in the U.S. in late December 2024. SPINRAZA royalties in 2024 compared to 2023 were impacted from an annual order from a single country that did not recur in 2024.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue decreased in 2024 compared to 2023 primarily due to the decrease in WAINUA joint development revenue as development
    activities relating to ATTRv-PN wound down with the commercial launch of WAINUA. In addition, R&amp;D revenue decreased due to the timing of significant partner payments.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">WAINUA (Eplontersen) Collaboration with AstraZeneca</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our financial results for the years ended December 31, 2024 and 2023 reflected the cost-sharing provisions related to our collaboration with AstraZeneca to develop and
    commercialize WAINUA for the treatment of ATTR. Under the terms of the collaboration agreement, AstraZeneca is currently paying 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading and
    conducting the Phase 3 development program, we are recognizing as R&amp;D revenue the 55 percent of cost-share funding AstraZeneca is responsible for, net of our share of AstraZeneca&#8217;s development expenses, in the same period we incur the related
    development expenses.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As AstraZeneca is responsible for the vast majority of the medical affairs and commercial costs in the U.S. and all costs associated with
    bringing WAINUA to market outside the U.S., we are recognizing cost-share funding we receive from AstraZeneca related to these activities as a reduction of our medical affairs and commercialization expenses, which we classify as R&amp;D and selling,
    general and administrative, or SG&amp;A, expenses, respectively. We expect our medical affairs and commercialization expenses to increase as WAINUA advances toward the market under our collaboration with AstraZeneca.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on revenue and expenses under this collaboration (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA joint development revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">126.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development expenses related to Phase 3 development expenses for WAINUA</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">107.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">150.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Medical affairs expenses for WAINUA</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercialization expenses for WAINUA</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our WAINUA joint development revenue in 2024 and 2023 includes a $30 million milestone payment from AstraZeneca that we earned when the
    MHRA approved WAINUA for ATTRv-PN in the UK as WAINZUA and a $50 million milestone payment from AstraZeneca that we earned when the FDA approved WAINUA for ATTRv-PN in the U.S., respectively.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Operating Expenses</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on operating expenses (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,050.0</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,035.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,180.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,141.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses, excluding non-cash compensation expense related to equity awards, increased slightly in 2024 compared to 2023.
    SG&amp;A expenses increased year over year primarily due to the launches of WAINUA and TRYNGOLZA, including establishing the TRYNGOLZA field team in the second quarter of 2024, and advancing launch preparation activities for donidalorsen. R&amp;D
    expenses were essentially flat year over year as several late-stage studies ended.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards increased in 2024 compared to 2023 due to increased headcount and a higher stock
    price on the grant date of annual equity awards in 2024 compared to 2023. We believe non-cash compensation expense related to equity awards is not indicative of our operating results or cash flows from our operations.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Cost of Sales</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, which consisted of manufacturing costs, including certain fixed
    costs, transportation and freight, indirect overhead costs primarily associated with the manufacturing and distribution of TRYNGOLZA, TEGSEDI and WAYLIVRA and certain associated period costs.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on cost of sales (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total cost of sales</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Research, Development and Patent Expenses</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and patent expenses consist of expenses for drug discovery, drug development, medical affairs, manufacturing and
    development chemistry and R&amp;D support expenses.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on research, development and patent expenses (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">809.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">821.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">92.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research, development and patent expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">901.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">899.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Drug Discovery</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use our proprietary technologies to generate information about the function of genes and to determine the value of genes as drug
    discovery targets. We use this information to direct our own drug discovery research, and that of our partners. Drug discovery is also the function that is responsible for advancing our core technology. This function is also responsible for making
    investments in complementary technologies to expand the reach of our technologies.</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on drug discovery expenses (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug discovery expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">114.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">125.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total drug discovery expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">132.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">141.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug discovery expenses, excluding non-cash compensation expense related to equity awards, decreased in 2024 compared to 2023. In 2023, we
    recognized $15 million in R&amp;D expense for licensing Vect-Horus&#8217; platform technology.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Drug Development</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth drug development expenses, including expenses for our marketed medicines and those in Phase 3 development
    for which we have incurred significant costs (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">103.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">115.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olezarsen</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">147.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">138.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Donidalorsen</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Zilganersen</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ulefnersen</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.0</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other development projects</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">89.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101.0</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Development overhead expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">135.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">123.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total drug development, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">527.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">530.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total drug development expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">568.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">564.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our development expenses, excluding non-cash compensation expense related to equity awards, were essentially flat in 2024 compared to
    2023. We expect our development expenses will continue to be stable as several late-stage studies end and we reallocate resources toward earlier stage programs.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may conduct multiple clinical trials on a drug candidate, including multiple clinical trials for the various indications we may be
    studying. Furthermore, as we obtain results from trials, we may elect to discontinue clinical trials for certain drug candidates in certain indications in order to focus our resources on more promising drug candidates or indications. Our Phase 1 and
    Phase 2 programs are clinical research programs that fuel our Phase 3 pipeline. When our medicines are in Phase 1 or Phase 2 clinical trials, they are in a dynamic state in which we may adjust the development strategy for each medicine. Although we may
    characterize a medicine as &#8220;in Phase 1&#8221; or &#8220;in Phase 2,&#8221; it does not mean that we are conducting a single, well-defined study with dedicated resources. Instead, we allocate our internal resources on a shared basis across numerous medicines based on
    each medicine&#8217;s particular needs at that time. This means we are constantly shifting resources among medicines. Therefore, what we spend on each medicine during a particular period is usually a function of what is required to keep the medicines
    progressing in clinical development, not what medicines we think are most important. For example, the number of people required to start a new study is large, the number of people required to keep a study going is modest and the number of people
    required to finish a study is large. However, such fluctuations are not indicative of a shift in our emphasis from one medicine to another and cannot be used to accurately predict future costs for each medicine. Because we always have numerous
    medicines in preclinical and varying stages of clinical research, the fluctuations in expenses from medicine to medicine, in large part, offset one another. If we partner a medicine, it may affect the size of a trial, its timing, its total cost and the
    timing of the related costs.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Medical Affairs</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our medical affairs function is responsible for funding and coordinating investigator-sponsored trials, communicating scientific and
    clinical information to healthcare providers, medical professionals and patients, and managing publications.</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on medical affairs expenses (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Medical affairs expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total medical affairs expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Medical affairs expenses, excluding non-cash compensation
      expense related to equity awards, increased in 2024 compared to 2023 as we continued advancing our late-stage pipeline</span>.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Manufacturing and Development Chemistry</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenditures in our manufacturing and development chemistry function consist primarily of personnel costs, specialized chemicals for
    oligonucleotide manufacturing, validation batches to support regulatory approvals, laboratory supplies and outside services. Our manufacturing and development chemistry function is responsible for providing drug supplies to drug development and our
    collaboration partners. Our manufacturing procedures include testing to satisfy good laboratory and good manufacturing practice requirements.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on manufacturing and development chemistry expenses (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Manufacturing and development chemistry expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total manufacturing and development chemistry expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Manufacturing and development chemistry expenses, excluding
      non-cash compensation expense related to equity awards, decreased in 2024 compared to 2023 due to the timing of manufacturing performed by our contract manufacturing organizations for drug product related to several late-stage programs. Refer to the
      section titled, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Manufacturing</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, in Part I, Item 1, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Business</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for further details on the activities and types of costs we incur
      in our manufacturing process.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">R&amp;D Support</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our research, development and patent expenses, we include support costs such as rent, repair and maintenance for buildings and
    equipment, utilities, depreciation of laboratory equipment and facilities, amortization of our intellectual property, information technology costs, procurement costs and waste disposal costs. We call these costs R&amp;D support expenses.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on R&amp;D support expenses (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Personnel costs</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Occupancy</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consulting</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patent expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Insurance</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software and licenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D support expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81.0</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.0</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D support expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">96.0</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D support expenses, excluding non-cash compensation expense related to equity awards, were essentially flat in 2024 compared to
    2023.</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Selling, General and Administrative Expenses</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SG&amp;A expenses include personnel and outside costs associated with the pre-commercialization and commercialization activities for our
    medicines and costs to support our company, our employees and our stockholders including, legal, human resources, investor relations and finance. Additionally, we include in SG&amp;A expenses such costs as rent, repair and maintenance of buildings and
    equipment, depreciation and utilities costs that we need to support the corporate functions listed above. We also include fees we owe under our in-licensing agreements related to SPINRAZA and QALSODY.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on SG&amp;A expenses (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">230.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">205.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37.0</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total selling, general and administrative expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">267.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">232.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SG&amp;A expenses, excluding non-cash compensation expense related to equity awards, increased in 2024 compared to 2023 due to the
    launches of WAINUA and TRYNGOLZA, including establishing the TRYNGOLZA field team in the second quarter of 2024, and advancing launch preparation activities for donidalorsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.
      We expect SG&amp;A expenses to increase as we continue to invest in our independent commercial launches.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Investment Income</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment income for 2024
    was $107.0 million compared to $89.0
    million for 2023. The increase in investment income was primarily due to an increase in interest rates associated with our investments during
    a majority of 2024 compared to 2023. In addition, our cash available for investing increased due to the $489.1 million net proceeds we received from our public common stock offering in September 2024. Refer to Part IV, Item 15, Note 8, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Stockholders&#8217; Equity</span>, in the Notes to the Consolidated Financial Statements for further details on the public offering.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Interest Expense</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on interest expense (in millions):</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible senior notes:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash amortization of debt issuance costs</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense payable in cash</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest on mortgage for primary R&amp;D and manufacturing facilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total interest expense</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.0</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Interest expense for </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> was $</span>17.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million compared to $</span>12.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In June 2023, we completed a $575.0 million offering of our 1.75% Notes and repurchased $504.4 million in principal of our 0.125% Notes.
      As a result, beginning in the second quarter of 2023, our interest expense related to our convertible notes included interest expense incurred for our 1.75% Notes. Interest expense in 2024 included a full year of interest expense related to our 1.75%
      Notes.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Interest Expense Related to Sale of Future Royalties</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recorded $</span>73.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>68.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of interest expense related to the sale of future royalties in 2024 and 2023, respectively. These amounts are related to the Royalty
      Pharma Investments, or Royalty Pharma, transaction, in which we sold a minority interest in our future SPINRAZA and pelacarsen royalties to Royalty Pharma for a $500 million upfront payment and $625 million of potential future payments. Refer to </span>Part
    IV, Item 15, Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the Notes to the Consolidated Financial Statements<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for further details.</span></div>

  <div><br/>
  </div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Loss on Investments</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded a $2.9 million and
    $1.9 million loss on investments for 2024 and 2023, respectively. The period-over-period fluctuation in our loss on investments was primarily
    driven by changes in the fair value of our investments in privately held and publicly traded biotechnology companies.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Other Income (Expense)</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2023, we completed a $575.0 million offering of our 1.75%
      Notes and used $488.2 million of the net proceeds to repurchase $504.4 million in principal of our 0.125% Notes. As a result of these repurchases, we recorded a $13.4 million gain on early retirement of debt in 2023, which reflects the difference
      between the amounts we paid to repurchase portions of our 0.125% Notes and the net carrying balance of the liability at the time that we repurchased the debt. Refer to </span>Part IV, Item 15, Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated Financial Statements for further
      details regarding our convertible debt.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Income Tax Expense (Benefit)</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded an income tax benefit of $6.2 million for 2024 compared to an income tax expense of $32.3 million for 2023.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The income tax benefit during 2024 primarily related to adjustments to prior year tax return positions for the royalty purchase agreement
    with Royalty Pharma and deductions related to foreign SPINRAZA royalties.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The decrease in income tax expense for 2024 compared to 2023 primarily related to the impact of the Royalty Pharma transaction in 2023. We
    reflected the Royalty Pharma transaction as a taxable sale, which required us to include the proceeds from the sale, net of currently deductible issuance costs, as taxable income in 2023.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We continue to maintain a full valuation allowance on all our net deferred tax assets.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Net Loss and Net Loss per Share</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generated a net loss of $453.9
    million for 2024 compared to $366.3
    million for 2023. Our net loss increased for 2024
    compared to 2023 primarily due to factors discussed in the sections above<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>Basic and diluted net loss per share for 2024 were $3.04 compared to $2.56 for 2023. Our net loss per share increased for 2024 compared to 2023 primarily due to factors discussed in the sections above.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Liquidity and Capital Resources</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have financed our operations primarily from research and
      development collaborative agreements. </span>We also financed our operations from commercial revenue from SPINRAZA royalties and TEGSEDI and WAYLIVRA commercial revenue. In addition, we began receiving commercial revenue from WAINUA royalties in
    2024. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From our inception through December 31, </span>2024, we
    have earned approximately $7.9 billion<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in revenue. We have also
      financed our operations through the sale of our equity securities, the issuance of long-term debt, the sale leaseback of facilities and the sale of future royalties. From the time we were founded through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have raised net proceeds of approximately $</span>2.6&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">billion from the sale of our equity securities, which includes our sale
      of 11.5 million shares of common stock for net proceeds of $489 million in September 2024. Additionally, from our inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have borrowed approximately $</span>2.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion under long-term debt arrangements and received proceeds of approximately $0.5 billion from the sale of future royalties to finance a portion of our operations.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our working capital increased from 2023 to 2024 primarily due to a decrease in current liabilities as a result of lower deferred contract
    revenue as of December 31, 2024 compared to December 31, 2023. During the same period, our long-term obligations did not change significantly.</div>

  <div><br/>
  </div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

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  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our contractual obligations, excluding our liability related to the sale of future royalties, as of December 31, 2024. The table provides a breakdown of when obligations become due. We provide a more detailed description of the major components of our
    debt in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Part IV, Item 15, Note 7, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and
      Commitments</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, in the </span>Notes to the Consolidated Financial Statements<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

  <div><br/>
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  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contractual Obligations</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Payments Due by Period</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in millions)</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(selected balances described below)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 1 year</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 1 year</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.75% Notes (principal and interest payable)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">610.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">600.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0% Notes (principal payable)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating leases</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">260.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">239.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building mortgage payments (principal and interest payable)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other obligations (principal and interest payable)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,513.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.6</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,481.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our contractual obligations consist primarily of our convertible debt. In addition, we also have a facility mortgage, facility leases,
    equipment financing arrangements and other obligations. We believe our cash, cash equivalents and short-term investments, as well as plans for cash in the future, will be sufficient to fund our planned operations and these obligations. We have not
    entered into, nor do we currently have, any off-balance sheet arrangements (as defined under SEC rules).</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Convertible Debt and Call Spread</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Refer to our Convertible Debt and Call Spread accounting
      policies in Part IV, Item 15, Note 1, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, and Note 7, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, in the Notes to the Consolidated Financial Statements for the significant terms of each convertible debt instrument.</span></div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Operating Facilities</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Part IV, Item 15, </span>Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated
      Financial Statements</span> for further details on our operating facilities.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Operating Leases</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Part IV, Item 15, </span>Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated
      Financial Statements</span> for further details on our operating leases<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Royalty Revenue Monetization</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2023, we entered into a royalty purchase agreement with Royalty Pharma to monetize a portion of our future SPINRAZA and pelacarsen
    royalties we are entitled to under our agreements with Biogen and Novartis, respectively. Refer to <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Part IV, Item 15, </span>Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated Financial Statements</span>
    for further details on this agreement.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Other Obligations</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to contractual obligations, we had outstanding purchase orders as of December 31, 2024 for the purchase of services, capital equipment and materials as part of our normal course of business.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may enter into additional collaborations with partners which could provide for additional revenue to us and we may incur additional
    cash expenditures related to our obligations under any of the new agreements we may enter into. We currently intend to use our cash, cash equivalents and short-term investments to finance our activities. However, we may also pursue other financing
    alternatives, like issuing additional shares of our common stock, issuing debt instruments, refinancing our existing debt, securing lines of credit or executing royalty monetization agreements. Whether we use our existing capital resources or choose to
    obtain financing will depend on various factors, including the future success of our business, the prevailing interest rate environment and the condition of financial markets generally.</div>

  <div><br/>
  </div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Critical Accounting Estimates</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the U.S. As such, we make
    certain estimates, judgments and assumptions that we believe are reasonable, based upon the information available to us. These judgments involve making estimates about the effect of matters that are inherently uncertain and may significantly impact our
    quarterly or annual results of operations and financial condition. Each quarter, our senior management reviews the development, selection and disclosure of such estimates with the audit committee of our board of directors. In the following paragraphs,
    we describe the specific risks associated with these critical accounting estimates and we caution that future events rarely develop exactly as one may expect, and that best estimates may require adjustment. Our significant accounting policies are
    outlined in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Part IV, Item 15, </span>Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant
      Accounting Policies</span>, in the Notes to the Consolidated Financial Statements.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are our significant accounting estimates, which we believe are the most critical to aid in fully understanding and
    evaluating our reported financial results:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Assessing the propriety of revenue recognition and associated deferred revenue;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Assessing the appropriate estimate of anticipated future royalty payments under our royalty purchase agreement</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are descriptions of our critical accounting estimates.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Revenue Recognition</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn revenue from several sources. The judgements and estimates we make vary between each source of our revenue. At contract inception,
    we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the
    commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>,
    or ASC 808. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and are therefore within the scope of ASC 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently
    apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of the critical accounting estimates we make with respect to our revenue.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaborative agreements</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize R&amp;D revenue from numerous collaboration agreements. Our collaboration agreements typically contain multiple elements, or
    performance obligations, including technology licenses or options to obtain technology licenses, R&amp;D services, and manufacturing services. Upon entering into a collaboration agreement, we are required to make the following judgements:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Identifying the performance obligations contained in the agreement</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our assessment of what constitutes a separate performance
      obligation requires us to apply judgement.</span> Specifically, we have to identify which goods and services we are required to provide under the contract are distinct.</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Determining the transaction price, including any variable consideration</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To determine the transaction price, we review the amount of consideration we are eligible to earn under the agreement. We do not typically
    include any payments we may receive in the future in our initial transaction price since the payments are typically not probable because they are contingent upon certain future events. We reassess the total transaction price at each reporting period to
    determine if we should include additional payments in the transaction price that have become probable.</div>

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    </div>

  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Allocating the transaction price to each of our performance obligations</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling
    price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. The estimate of the relative stand-alone selling price requires us in some cases to make significant judgements. For example, when we
    deliver a license at the start of an agreement, we use valuation methodologies, such as the relief from royalty method, to value the license. Under this method we are required to make estimates including future sales, royalties on future product sales,
    contractual milestones, expenses, income taxes and discount rates. Additionally, when we estimate the selling price for R&amp;D services, we make estimates, including: the number of internal hours we will spend on the services, the cost of work we and
    third parties will perform and the cost of clinical trial material we will use.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The R&amp;D revenue we recognize each period is comprised of several types of revenue, including amortization from upfront payments,
    milestone payments, license fees and other services that we recognize immediately or amortize over the period in which we satisfy our performance obligation. Each of these types of revenue require us to make various judgements and estimates.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">R&amp;D Services with Upfront Payments</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize revenue from the amortization of upfront payments as we perform R&amp;D services. We use an input method to estimate the
    amount of revenue to recognize each period. This method requires us to make estimates of the total costs we expect to incur to complete our R&amp;D services performance obligation or the total amount of effort it will take us to complete our R&amp;D
    services performance obligation. If we change our estimates, we may have to adjust our revenue.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Milestone Payments</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When recognizing revenue related to milestone payments, we typically make the following judgements and estimates:</div>

  <div><br/>
  </div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether a milestone payment is probable (discussed in detail above under &#8220;Determining the<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
              transaction price, including any variable consideration&#8221;</span>); and</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we are performing services, we recognize revenue over our estimated period of performance in a similar manner to the amortization of upfront payments (discussed above
            under &#8220;R&amp;D Services with Upfront Payments&#8221;).</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">License Fees</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we grant a license for a medicine in clinical
      development, we generally recognize as R&amp;D revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. Refer to Part IV, Item 15, Note 1, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated Financial Statements</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for our revenue recognition policy. We discuss
      the estimates we make related to the relative stand-alone selling price of a license in detail above under &#8220;Allocating the transaction price to each of our performance obligations.&#8221;</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Estimated Liability for Clinical Development Costs</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly
    basis, we estimate our liability for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to
    third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities
    determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon
    settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024, a
    hypothetical 10 percent increase in our liability for preclinical and clinical development costs would have resulted in an increase in our loss before income tax benefit and accrued liabilities of approximately $7.7 million.</div>

  <div><br/>
  </div>

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    </div>

  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Liability Related to Sale of Future Royalties</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2023, we entered into a royalty purchase agreement with Royalty Pharma to monetize a portion of our future SPINRAZA and pelacarsen
    royalties we are entitled to under our agreements with Biogen and Novartis, respectively. Under our agreement with Royalty Pharma, we calculate the liability related to the sale of future royalties, effective interest rate and the related interest
    expense using our current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. The
    amount that Royalty Pharma will receive under the agreement is based on sales of SPINRAZA, our currently commercialized medicine, and pelacarsen, a product candidate that is not currently commercialized. As such, the repayment amounts that we estimate
    related to projections of future pelacarsen revenues contain more subjective estimation which we believe could lead to larger changes in estimates in the future. If there is a material change in our estimate, we will prospectively adjust the effective
    interest rate and the related interest expense.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of future royalty
    payments, particularly those from Novartis for pelacarsen, and could result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the regulatory approval and commercial sales of
    pelacarsen, competing products or other significant events. These factors and other events or circumstances could result in reduced royalty payments from sales of pelacarsen, which would result in a reduction of our non-cash royalty revenue and
    non-cash interest expense over the life of the agreement. Conversely, if sales of pelacarsen are more than amounts we estimated, the non-cash royalty revenue and non-cash interest expense we record would be greater over the life of the arrangement.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item7A"><!--Anchor--></a>Item 7A. Quantitative and Qualitative Disclosures About Market Risk</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are exposed to changes in interest rates primarily from
      our investments in certain short-term investments. We primarily invest our excess cash in highly liquid short-term investments of the U.S. Treasury and reputable financial institutions, corporations, and U.S. government agencies with strong credit
      ratings. We typically hold our investments for the duration of the term of the respective instrument. We do not utilize derivative financial instruments, derivative commodity instruments or other market risk sensitive instruments, positions or
      transactions to manage exposure to interest rate changes. Accordingly, we believe that, while the securities we hold are subject to changes in the financial standing of the issuer of such securities, we were not subject to any material risks arising
      from changes in interest rates, foreign currency exchange rates, commodity prices, equity prices or other market changes that affect market risk sensitive instruments as of </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and will not be subject to any material risks arising from these changes in the
      foreseeable future</span>.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item8"><!--Anchor--></a>Item 8. Financial Statements and Supplementary Data</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We filed our consolidated financial statements and supplementary data required by this item as exhibits hereto, and listed them under Item
    15(a)(1) and (2), and incorporate them herein by reference.</div>

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    </div>

  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 9<a id="Item9"><!--Anchor--></a>. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">None.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item9A"><!--Anchor--></a>Item 9A. Controls and Procedures</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Disclosure Controls and Procedures</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We maintain disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as
    amended, or Exchange Act) that are designed to ensure that information we are required to disclose in our Exchange Act reports is recorded, processed, summarized and reported within the time periods specified in the SEC&#8217;s rules and forms, and that such
    information is accumulated and communicated to our management, including our Chief Executive Officer and Chief Financial Officer, as appropriate, to allow timely decisions regarding required disclosure. We designed and evaluated our disclosure controls
    and procedures recognizing that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance and not absolute assurance of achieving the desired control objectives.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of the end of the period covered by this report on Form 10-K, we carried out an evaluation of our disclosure controls and procedures
    under the supervision of, and with the participation of our management, including our Chief Executive Officer and Chief Financial Officer. Based on our evaluation, our Chief Executive Officer and Chief Financial Officer concluded that our disclosure
    controls and procedures were effective as of December 31, 2024.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Management</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s Report on Internal Control over Financial Reporting</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our management is responsible for establishing and maintaining adequate internal control over financial reporting, as defined in Exchange
    Act Rules 13a-15(f). Our internal control over financial reporting is a process designed under the supervision of our Chief Executive Officer and Chief Financial Officer to provide reasonable assurance regarding the reliability of financial reporting
    and the preparation of our financial statements for external purposes in accordance with U.S. generally accepted accounting principles.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024, we
    assessed the effectiveness of our internal control over financial reporting based on the criteria for effective internal control over financial reporting under the 2013 &#8220;Internal Control&#8212;Integrated Framework,&#8221; issued by the Committee of Sponsoring
    Organizations, or COSO, of the Treadway Commission, under the supervision of, and with the participation of our management, including our Chief Executive Officer and Chief Financial Officer. Based on that assessment, our management concluded that we
    maintained effective internal control over financial reporting as of December 31, 2024.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ernst &amp; Young LLP, an independent registered public accounting firm, audited the effectiveness of our internal control over financial
    reporting as of December 31, 2024, as stated in their attestation report, which is included elsewhere herein.</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Changes in Internal Control over Financial Reporting</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The above assessment did not identify any change in our internal control over financial reporting that occurred during our latest fiscal
    quarter and that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.</div>

  <div><br/>
  </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM</div>

  <div><br/>
  </div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To the Stockholders and the Board of Directors of Ionis Pharmaceuticals, Inc.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Opinion on Internal Control Over Financial Reporting</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have audited Ionis Pharmaceuticals, Inc.&#8217;s internal control over financial reporting as of December 31, 2024, based on criteria established in Internal
    Control&#8212;Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) (the COSO criteria). In our opinion, Ionis Pharmaceuticals, Inc. (the Company) maintained, in all material respects, effective
    internal control over financial reporting as of December 31, 2024, based on the COSO criteria.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the consolidated balance
    sheets of the Company as of December 31, 2024 and 2023, the related consolidated statements of operations, comprehensive loss, stockholders&#8217; equity and cash flows for each of the three years in the period ended December 31, 2024, and the related notes
    and our report dated February 19, 2025 expressed an unqualified opinion thereon.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis for Opinion</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The Company&#8217;s management is responsible for maintaining effective internal control over financial reporting and for its assessment of the effectiveness of
    internal control over financial reporting included in the accompanying Management&#8217;s Report on Internal Control over Financial Reporting. Our responsibility is to express an opinion on the Company&#8217;s internal control over financial reporting based on our
    audit. We are a public accounting firm registered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange
    Commission and the PCAOB.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We conducted our audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable
    assurance about whether effective internal control over financial reporting was maintained in all material respects.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, testing and
    evaluating the design and operating effectiveness of internal control based on the assessed risk, and performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our
    opinion.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Definition and Limitations of Internal Control Over Financial Reporting</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A company&#8217;s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting
    and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company&#8217;s internal control over financial reporting includes those policies and procedures that (1) pertain to the
    maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit preparation of
    financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (3) provide
    reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of the company&#8217;s assets that could have a material effect on the financial statements.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation
    of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ Ernst &amp; Young LLP</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">San Diego, California</div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>

  <div><br/>
  </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item9B"><!--Anchor--></a>Item 9B. Other Information</div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Trading Plans</div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="ecd:MtrlTermsOfTrdArrTextBlock" id="Text_1aa67457e56b43c98425cbbb56b8a66f" contextRef="c20240101to20241231" escape="true" continuedAt="Text_d0d46132be6b4cd18880791fc096ae151">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the quarter ended December 31, 2024, our
    directors and officers (as defined in Rule 16a-1(f) under the Exchange Act), or Section 16 officers and directors, adopted or terminated contracts, instructions or written plans for the purchase or sale of our securities as noted in the table below.</div>
</ix:nonNumeric>

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  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Contract, instruction or written plan intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) under the Exchange Act.</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">**</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8220;Non-Rule 10b5-1 trading arrangement&#8221; as defined in item 408(c) of Regulation S-K under the Exchange Act.</div>
        </td>

  </tr>


</table>
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  <tr>

    <td rowspan="2" style="width: 22%; vertical-align: bottom;"> </td>

    <td rowspan="2" style="width: 1%; vertical-align: bottom;">&#160;</td>

    <td rowspan="2" style="width: 10%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Action</div>
        </td>

    <td rowspan="2" style="width: 0.66%; vertical-align: bottom;">&#160;</td>

    <td rowspan="2" style="width: 15.54%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Date</div>
        </td>

    <td rowspan="2" style="width: 1.21%; vertical-align: bottom;">&#160;</td>

    <td colspan="3" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Trading Arrangement</div>
        </td>

    <td rowspan="2" style="width: 1.06%; vertical-align: bottom;">&#160;</td>

    <td rowspan="2" style="width: 9.83%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Shares</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> to be Sold</div>
        </td>

    <td rowspan="2" style="width: 0.93%; vertical-align: bottom;">&#160;</td>

    <td rowspan="2" style="width: 16%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration Date</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Rule 10b5-1*</div>
        </td>

    <td style="width: 1.46%; vertical-align: bottom; border-top: #000000 2px solid;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="ecd:NonRule10b51ArrAdoptedFlag" id="Fact_c1c2e177e03f4cd98895b874e54eec96" contextRef="c20241001to20241231" format="ixt:fixed-false">Non-Rule 10b5-1</ix:nonNumeric>**</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; vertical-align: bottom; background-color: rgb(204, 238, 255);">
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        </td>

    <td style="width: 1%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_4da096b126c946ab97fa70bd9a39f088">Adoption</span></div>
        </td>

    <td style="width: 0.66%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 15.54%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
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        </td>

    <td style="width: 1.21%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="ecd:Rule10b51ArrAdoptedFlag" id="Fact_085e371429e24bf5b4c7a2c6e0f9daff" contextRef="c20241001to20241231" format="ixt:fixed-true">X</ix:nonNumeric></div>
        </td>

    <td style="width: 1.46%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 1.06%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.83%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ecd:TrdArrSecuritiesAggAvailAmt" id="Fact_ea1b960ab6c3459d82d4b0ff3d948f50" contextRef="c20241231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">104,079</ix:nonFraction></div>
        </td>

    <td style="width: 0.93%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 16%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="ecd:TrdArrExpirationDate" id="Fact_ee09332875e04df39fe1bd78df838f4b" contextRef="c20241001to20241231">February 28, 2026</ix:nonNumeric></div>
        </td>

  </tr>


</table>
</ix:continuation></div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item9C"><!--Anchor--></a>Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="PARTIII"><!--Anchor--></a>PART III</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item10"><!--Anchor--></a>Item 10. Directors, Executive Officers and Corporate Governance</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We incorporate by reference the information required by this
      Item with respect to directors and the Audit Committee from the information under the caption &#8220;ELECTION OF DIRECTORS,&#8221; including in particular the information under &#8220;Nominating, Governance and Review Committee&#8221; and &#8220;Audit Committee,&#8221; contained in our
      definitive Proxy Statement, which we will file with the Securities and Exchange Commission within 120 days after the end of the fiscal year ended </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Proxy Statement.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We include information concerning our executive officers in the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Information about our Executive Officers</span>, in this report on the Form 10-K in Part I, Item 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Business</span>.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the required information concerning our Code of Ethics from the information under the caption &#8220;Code of Ethics
    and Business Conduct&#8221; contained in the Proxy Statement. Our Code of Ethics and Business Conduct is posted on our website at www.ionispharma.com<sup>(1)</sup>. We intend to make all required disclosures regarding any amendments to, or waivers from,
    provisions of our Code of Ethics and Business conduct on our website.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The Company has adopted insider trading policies and procedures governing the purchase, sale and other dispositions of the Company&#8217;s
    securities by its directors, officers and employees that are reasonably designed to promote compliance with insider trading laws, rules and regulations, and any listing standards applicable to the Company. In addition, it is the Company&#8217;s practice to
    comply with both the letter and the spirit of applicable laws and regulations relating to insider trading.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by item 402(x) to the information under the caption &#8220;Policies and practices related
    to the grant of certain equity awards close in time to the release of material nonpublic information&#8221; contained in the Proxy Statement.</div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">___________</div>

  <div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; text-align: right;">
            <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</div>
          </td>

    <td style="width: auto; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Any information that is included on or linked to our website is not part of this Form 10-K.</div>
          </td>

  </tr>


</table>
  </div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Delinquent Section 16(a) Reports</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Part I, Item 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Business</span>, of this
    Report contains information concerning our executive officers. We incorporate by reference the information required by this Item concerning compliance with Section 16(a) of the Exchange Act from the information under the caption &#8220;Delinquent Section
    16(a) Reports&#8221; contained in the Proxy Statement.</div>

  <div><br/>
  </div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 11<a id="Item11"><!--Anchor--></a>. Executive Compensation</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by this item to the information under the caption &#8220;EXECUTIVE COMPENSATION,&#8221;
    &#8220;Compensation Committee Interlocks and Insider Participation&#8221; and &#8220;COMPENSATION COMMITTEE REPORT&#8221; contained in the Proxy Statement.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by Item 402(x) of Regulation S-K to the information under the caption &#8220;Policies and
    practices related to the grant of certain equity awards close in time to the release of material nonpublic information&#8221; contained in the Proxy Statement.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item12"><!--Anchor--></a>Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by this item to the information under the captions &#8220;SECURITY OWNERSHIP OF CERTAIN
    BENEFICIAL OWNERS AND MANAGEMENT&#8221; contained in the Proxy Statement.</div>

  <div><br/>
  </div>

  <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Securities Authorized for Issuance under Equity Compensation Plans</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information regarding outstanding options and shares reserved for future issuance under our equity
    compensation plans as of December 31, 2024.</div>

  <div style="text-align: left;"><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 41.45%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Plan Category</div>
        </td>

    <td style="width: 1%; vertical-align: bottom;">&#160;</td>

    <td style="border-bottom: 2px solid; vertical-align: bottom; white-space: nowrap; width: 19.85%;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of Shares to</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">be Issued Upon Exercise</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Outstanding Options</div>
        </td>

    <td style="vertical-align: bottom; white-space: nowrap; width: 0.75%;">&#160;</td>

    <td colspan="2" style="border-bottom: 2px solid; vertical-align: bottom; white-space: nowrap; width: 17.48%;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exercise Price of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Outstanding Options</div>
        </td>

    <td style="vertical-align: bottom; white-space: nowrap; width: 0.87%;">&#160;</td>

    <td style="border-bottom: 2px solid; vertical-align: bottom; white-space: nowrap; width: 16.36%;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of Shares</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Remaining Available</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">for Future Issuance</div>
        </td>

    <td style="width: 2.24%; vertical-align: bottom;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 41.45%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity compensation plans approved by stockholders (a)</div>
        </td>

    <td style="width: 1%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19.85%; vertical-align: bottom; border-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,717,114</div>
        </td>

    <td style="width: 0.75%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 2.87%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td style="width: 14.61%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.23</div>
        </td>

    <td style="width: 0.87%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 16.36%; vertical-align: bottom; border-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,800,341</div>
        </td>

    <td style="width: 2.24%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(b)</div>
        </td>

  </tr>

  <tr>

    <td style="width: 41.45%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td style="width: 1%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19.85%; vertical-align: bottom; border-bottom: #000000 4px double; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,717,114</div>
        </td>

    <td style="width: 0.75%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 2.87%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td style="width: 14.61%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.43</div>
        </td>

    <td style="width: 0.87%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 16.36%; vertical-align: bottom; border-bottom: #000000 4px double; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,800,341</div>
        </td>

    <td style="width: 2.24%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>


</table>
  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(a)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consists of five Ionis plans: 1989 Stock Option Plan, Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan, 2011 Equity Incentive Plan, 2020 Equity
            Incentive Plan and Employee Stock Purchase Plan, or ESPP.</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(b)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Of these shares, 270,482 were available for purchase under the ESPP as of December 31, 2024.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For additional details about our equity compensation plans, including a description of each plan, refer to Part IV, Item 15, Note 8, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Stockholders&#8217; Equity</span>, in the Notes to the Consolidated Financial Statements.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item13"><!--Anchor--></a>Item 13. Certain Relationships and Related Transactions, and Director Independence</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by this item to the information under the captions &#8220;Information Regarding the Board
    and Corporate Governance&#8221; and &#8220;Certain Relationships and Related Transactions&#8221; contained in the Proxy Statement.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item14"><!--Anchor--></a>Item 14. Principal Accountant Fees and Services</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by this item to the information under the caption &#8220;Ratification of Selection of
    Independent Auditors&#8221; contained in the Proxy Statement.</div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="PARTIV"><!--Anchor--></a>PART IV</div>

  <div style="text-align: center;"><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item15"><!--Anchor--></a>Item 15. Exhibits, Financial Statement Schedules</div>

  <div style="text-align: left;"><br/>
  </div>

  <div style="text-align: left; text-indent: -36pt; margin-left: 72pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(a)(1) Index to Financial Statements</div>

  <div style="text-align: justify; text-indent: -36pt; margin-left: 72pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We submitted the consolidated financial statements required by this item in a separate section beginning on page F-1 of this Report.</div>

  <div style="text-align: left; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: left; text-indent: -36pt; margin-left: 72pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(a)(2) Index to Financial Statement Schedules</div>

  <div style="text-align: left; text-indent: -36pt; margin-left: 72pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We omitted these schedules because they are not required, or are not applicable, or the required information is shown in the consolidated
    financial statements or notes thereto.</div>

  <div style="text-align: left; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: left; text-indent: -36pt; margin-left: 72pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(a)(3) Index to Exhibits</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">INDEX TO EXHIBITS</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10.71%; vertical-align: bottom;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit Number</div>
        </td>

    <td style="width: 2.13%; vertical-align: bottom;">&#160;</td>

    <td style="width: 87.16%; vertical-align: bottom;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Document</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000119312520235408/d75253dex21.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Agreement and Plan of Merger, dated as of August 30, 2020, among Akcea Therapeutics, Inc., Ionis Pharmaceuticals, Inc. and Avalanche Merger Sub, Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed August 31, 2020 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.1</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000047/exhibit3_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amended and Restated Certificate of Incorporation filed June 19, 1991</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for
              the year ended December 31, 2017 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.2</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036114017588/formdef14a.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certificate of Amendment to Restated Certificate of Incorporation</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an appendix to the Registrant&#8217;s Notice of 2014 Annual Meeting of
              Stockholders and Proxy Statement filed on April 25, 2014 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.3</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036115045083/ex3_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certificate of Amendment to Restated Certificate of Incorporation</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed December 18,
              2015 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.4</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036121010402/brhc10022399_ex3-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amended and Restated Bylaws</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed March 29, 2021 and incorporated
              herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.1</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000079/exhibit4-11.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Description of the Registrant&#8217;s Securities</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31,
              2021 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.2</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000091205700053343/a2032851zex-4_2.txt" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certificate of Designation of the Series C Junior Participating Preferred Stock</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to Registrant&#8217;s Current Report on Form 8-K
              filed December 13, 2000 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.3</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000047/exhibit4_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Specimen Common Stock Certificate</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2017 and
              incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.4</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036119022393/ex99_3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Warrant Transactions Confirmation for Convertible Senior Notes due 2024</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form
              8-K filed December 12, 2019 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.5</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000119312521113586/d158901dex41.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indenture, dated as of April 12, 2021, by and between the Registrant and U.S. Bank National Association, as trustee, including Form of 0 percent Convertible Senior Note due 2026</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed April 13, 2021 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000119312521113586/d158901dex102.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Warrant Confirmation for Convertible Senior Notes due 2026</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed
              April 13, 2021 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000119312521113586/d158901dex101.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Convertible Note Hedge Confirmation for Convertible Senior Notes due 2026</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on
              Form 8-K filed April 13, 2021 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.8</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000119312523165273/d511748dex41.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indenture, dated as of June 12, 2023, by and between the Registrant and U.S. Bank Trust Company, a National Association, as trustee, including Form of 1.75 percent Global Note due in 2028</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed June 12, 2023 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.1<span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">*</span></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401524000142/ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Advisory Services Agreement by and between the Registrant and Onaiza Cadoret-Manier dated March 15, 2024</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the
              Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.2*</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000136/ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Second Amended Non-Employee Director Compensation Policy</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter
              ended March 31, 2023 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.3*</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000104/ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Registrant&#8217;s Amended and Restated Severance Benefit Plan dated March 17, 2022</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on form
              10-Q for the quarter ended March 31, 2022 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.4</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401524000116/exhibit10-3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Indemnity Agreement entered into between the Registrant and its Directors and Executive Officers with related schedule</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an
              exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2023 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.5</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000047/exhibit10_4.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Employee Confidential Information and Inventions Agreement</a>, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2017 and incorporated herein by reference.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.6*</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036119005627/ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Registrant&#8217;s Amended and Restated 2000 Employee Stock Purchase Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to Registrant&#8217;s Current Report on Form 8-K filed on
              March 26, 2019 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.7*</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000136/ex10-2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Registrant&#8217;s Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan, </a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">filed as an exhibit to the Registrant&#8217;s Quarterly Report on
              Form 10-Q for the quarter ended March 31, 2023 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-10.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Option Agreement for Options granted under the Ionis Pharmaceuticals, Inc. Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2022 and incorporated herein by reference.</span></div>
        </td>

  </tr>


</table>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9*</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000136/ex10-3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Forms of Restricted Stock Unit Grant Notice and Restricted Stock Unit Agreement for Restricted Stock Units granted under the Ionis Pharmaceuticals, Inc. Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan, </a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2023 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.10*</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/ix?doc=/Archives/edgar/data/874015/000114036124022103/ny20009042x1_def14a.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amended and Restated Ionis Pharmaceuticals, Inc. 2011 Equity Incentive Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an appendix to the Registrant&#8217;s Notice of
              2024 Annual Meeting of Stockholders and Proxy Statement filed on April 25, 2024 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.11<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-13.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Option Agreement under the 2011 Equity Incentive Plan</a>, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year
              ended December 31, 2022 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.12<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-14.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Time-Vested Restricted Stock Unit Agreement for Restricted Stock Units granted under the 2011 Equity Incentive Plan</a>, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">filed as an
              exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2022 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.13*</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000079/exhibit10-19.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Forms of Performance Based Restricted Stock Unit Grant Notice and Performance Based Restricted Stock Unit Agreement for Performance Based Restricted Stock Units granted prior to January 1, 2023 under the 2011 Equity
              Incentive Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2021 and incorporated herein by
            reference.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.14<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-16.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Forms of Performance Based Restricted Stock Unit Grant Notice and Performance Based Restricted Stock Unit Agreement for Performance Based Restricted Stock Units granted beginning January 1, 2023 under the 2011 Equity
              Incentive Plan</a>, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2022 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.15*</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120030055/brhc10018560_ex99-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Registration Statement on Form S-8 filed
              on December 31, 2020 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.16*</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120030055/brhc10018560_ex99-2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Global Option Agreement for options granted under the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an
              exhibit to the Registrant&#8217;s Registration Statement on Form S-8 filed on December 31, 2020 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.17*</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120030055/brhc10018560_ex99-3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Global Restricted Stock Unit Agreement for restricted stock units granted under the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Registration Statement on Form S-8 filed on December 31, 2020 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.18*</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120030055/brhc10018560_ex99-4.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Forms of Restricted Stock Unit Grant Notice, Stock Option Grant Notice and Stock Option Exercise Notice for options granted under the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Registration Statement on Form S-8 filed on December 31, 2020 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.19</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036117028398/ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loan Agreement between Ionis Faraday, LLC and UBS AG</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> dated July 18, 2017, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K
              filed July 21, 2017 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.20</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036117028398/ex10_4.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Guaranty between the Registrant and UBS AG dated July 18, 2017</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed July
              21, 2017 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.21</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-24.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchase and Sale Agreement between Ionis Gazelle, LLC and 2850 2855 &amp; 2859 Gazelle Owner (DE) LLC dated as of October 20, 2022</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as
              an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2022 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the
              Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.22</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-25.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchase and Sale Agreement between the Registrant and Oxford I Asset Management USA Inc. dated as of October 20, 2022</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to
              the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2022 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant
              treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.23</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000186/ex10-2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">First Amendment dated June 15, 2023 to the Purchase and Sale Agreement by and between the Registrant and Oxford I Asset Management USA Inc. dated as of October 20, 2022</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2023 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.24</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-26.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lease Agreement dated October 20, 2022 between the Registrant and 2850 2855 &amp; 2859 Gazelle Owner (DE) LLC,</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> filed as an exhibit to the
              Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2022 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats
              as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.25</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000209/ex10-2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amended and Restated Lease Agreement between the Registrant and Lots 21 &amp; 22 Owner (DE) LLC dated as of August 21, 2023</a>, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended
            September 30, 2023 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the
              Registrant treats as private or confidential.</span></div>
        </td>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.26</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401524000116/exhibit10-25.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">First Amendment dated as of November 6, 2023 to Amended and Restated Lease Agreement between the Registrant and Lots 21 &amp; 22 Owner (DE) LLC dated as of August 21, 2023</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2023 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.27</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401524000187/ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Second Amendment dated as of June 11, 2024 to the Amended and Restated Lease Agreement by and between the Registrant and Lots 21 and 22 Owner (DE) LLC dated as of August 21, 2023</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 and incorporated </span>herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.28</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-27.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Defeasance Pledge and Security Agreement dated as of October 20, 2022 by and among Ionis Gazelle, LLC, Wells Fargo Bank, National Association, as Trustee for the Benefit of the Registered Holders of UBS Commercial Mortgage
              Trust 2017-C3, Commercial Mortgage Pass-Through Certificates, Series 2017-C3, and U.S. Bank Trust Company, National Association</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the
              Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2022 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats
              as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.29</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-28.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Defeasance Assignment, Assumption and Release Agreement dated as of October 20, 2022 by and among Ionis Gazelle, LLC, DHC UBSCM 17 C3 Successor Borrower-R, LLC, Wells Fargo Bank, National Association, as Trustee for the
              Benefit of the Registered Holders of UBS Commercial Mortgage Trust 2017-C3, Commercial Mortgage Pass-Through Certificates, Series 2017-C3, Midland Loan Services, a division of PNC Bank, National Association, and U.S. Bank Trust Company,
              National Association</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2022 and incorporated herein by
              reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.30</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-29.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Defeasance Account Agreement dated as of October 20, 2022 by and among Ionis Gazelle, LLC, U.S. Bank Trust Company, National Association, U.S. Bank National Association, as Trustee for the Benefit of the Registered Holders
              of UBS Commercial Mortgage Trust 2017-C3, Commercial Mortgage Pass-Through Certificates, Series 2017-C3, and Midland Loan Services, a division of PNC Bank, National Association</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2022 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material
              and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.31</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401514000095/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exclusive License Agreement between the Registrant and the University of Massachusetts dated January 14, 2010</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the
              Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2014 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant
              treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.32</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000110465910026849/a10-5958_1ex10d5.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, Development and License Agreement between the Registrant and Glaxo Group Limited dated March 30, 2010</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the
              Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2010 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.33</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000110465911044376/a11-13864_1ex10d1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #1 to the Research, Development and License Agreement dated May 11, 2011 by and between the Registrant and Glaxo Group Limited</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">,
              filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2011 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for
              confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.34</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000110465913016208/a12-28450_1ex10d44.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #2 to the Research, Development and License Agreement by and between the Registrant and Glaxo Group Limited dated October 30, 2012</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2012 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a
              request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.35</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036114030549/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No. 3 to the Research, Development and License Agreement by and between the Registrant and Glaxo Group Limited dated July 10, 2013</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">,
              filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2014 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for
              confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.36</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036114030549/ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #4 to the Research, Development and License Agreement by and between the Registrant and Glaxo Group Limited dated April 10, 2014</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">,
              filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2014 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for
              confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.37</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036114030549/ex10_3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #5 to the Research, Development and License Agreement by and between the Registrant, Glaxo Group Limited and GlaxoSmithKline Intellectual Property Development Limited dated June 27, 2014</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2014 and incorporated herein by reference. Portions of this exhibit have been omitted
              and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.38</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000082/ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #6 to Research, Development and License Agreement by and between the Registrant, Glaxo Group Limited and GlaxoSmithKline Intellectual Property Development Limited dated September 2, 2015</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and incorporated herein by reference. Portions of this exhibit have been
              omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>


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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

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    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.39</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401516000118/ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #7 to the Research, Development and License Agreement by and between the Registrant, Glaxo Group Limited and GlaxoSmithKline Intellectual Property Development Limited dated March 4, 2016</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2016 and incorporated herein by reference. Portions of this exhibit have been omitted
              and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.40</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000130/ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #8 to the Research, Development and License Agreement by and between the Registrant, Glaxo Group Limited and Glaxosmithkline Intellectual Property Development Limited, dated July 29, 2019</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 and incorporated herein by reference. Portions of this exhibit have been
              omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.41</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401514000095/ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amended and Restated Collaboration and License Agreement between the Registrant and Cold Spring Harbor Laboratory dated October 26, 2011</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed
              as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2014 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type
              that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.42</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401514000095/ex10_3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment to Amended and Restated Collaboration and License Agreement between the Registrant and Cold Spring Harbor Laboratory dated March 14, 2014</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2014 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material
              and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.43</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000110465912034636/a12-6491_1ex10d1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Development, Option and License Agreement between the Registrant and Biogen Idec International Holding Ltd. dated January 3, 2012</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an
              exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2012 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the
              Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.44</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036115009498/exhibit10_59.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #1 to the Development, Option and License Agreement between the Registrant and Biogen Idec International Holding Ltd. dated December 15, 2014</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2014 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii)
              the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.45</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000110465913016208/a12-28450_1ex10d45.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated December 7, 2012</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit
              to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2012 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.46</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000110465913081234/a13-19600_1ex10d2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #1 to Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated August 13, 2013</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed
              as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2013 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for
              confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.47</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036115009498/exhibit10_61.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No.2 to the Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated October 15, 2014</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed
              as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2014 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for
              confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.48</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401516000118/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No.3 to the Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated January 18, 2016</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed
              as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2016 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for
              confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.49</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000045/exhibit10_70.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No. 4 to the Collaboration, License and Development Agreement by and between the Registrant and AstraZeneca AB dated October 18, 2018</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">,
              filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2018 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for
              confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.50</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000110465913060361/a13-13715_1ex10d1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">HTT Research, Development, Option and License Agreement among the Registrant, F. Hoffmann-La Roche Ltd and Hoffman-La Roche Inc. dated April 8, 2013</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2023 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not
              material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.51</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000057/ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #1 to HTT Research, Development, Option and License Agreement between the Registrant, F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. dated January 9, 2015</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2015 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i)
              not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>


</table>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.52</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000057/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Second Amended and Restated Strategic Collaboration and License Agreement between the Registrant and Alnylam Pharmaceuticals, Inc. dated January 8, 2015</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2015 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and
              (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.53</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000082/ex10_3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment Number One to the Second Amended and Restated Strategic Collaboration and License Agreement between the Registrant and Alnylam Pharmaceuticals, Inc. dated July 13, 2015</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and incorporated herein by reference. Portions of this exhibit have been omitted and separately
              filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.54</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000082/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Strategic Collaboration Agreement between the Registrant and AstraZeneca AB dated July 31, 2015</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s
              Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.55</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000045/exhibit10_69.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No. 1 to the Strategic Collaboration Agreement by and between the Registrant and AstraZeneca AB, dated October 18, 2018</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an
              exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2018 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential
              treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.56</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401520000115/ex10_2.htm"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Amendment No. 2 dated April 30, </span>2020<span style="text-decoration: underline;"> to the Strategic Collaboration Agreement by and between the Registrant and AstraZeneca AB dated July 31, 2015</span></span></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not
              material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.57</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401521000056/exhibit10_79.htm"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Amendment No. 3 dated December 17, </span>2020<span style="text-decoration: underline;"> to the Strategic Collaboration Agreement by and between the Registrant and AstraZeneca AB dated July 31, 2015</span></span></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2020 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both
              (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="exhibit10-58.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.58</a></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Amendment No. 4 dated December 23, 2024 to the Strategic
                Collaboration Agreement by and between the Registrant and AstraZeneca AB dated July 31, 2015.</span> Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or
              confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.59</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/1662524/000104746917001995/a2231300zex-10_7.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Strategic Collaboration, Option and License Agreement by and among Akcea Therapeutics, Inc. and Novartis Pharma AG, dated January 5, 2017</a>, filed as an exhibit to Akcea Therapeutics, Inc.&#8217;s Form S-1 filed March 27,
            2017 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.60</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/1662524/000156459019018117/akca-ex101_176.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No. 1 to the Strategic Collaboration, Option and License Agreement between Akcea Therapeutics, Inc. and Novartis Pharma AG dated February 22, 2019</a>, filed as an exhibit to Akcea Therapeutics, Inc.&#8217;s Quarterly
            Report on Form 10-Q for the quarter ended March 30, 2019 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.61</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401517000033/ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock Purchase Agreement among the Registrant, Akcea Therapeutics, Inc. and Novartis Pharma AG</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> dated January 5, 2017, filed as an exhibit to
              the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2017 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.62</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000047/exhibit10_17.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research Collaboration, Option and License Agreement between the Registrant and Biogen MA Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> dated December 19, 2017, filed as an exhibit to
              the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2017 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.63</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000105/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">New Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, dated April 19, 2018, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed
              with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.64</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000130/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No. 1 to the New Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement between the Registrant and Biogen MA Inc., dated August 16, 2019</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 and incorporated herein by reference. Portions of this exhibit have been omitted
              because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>


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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">80</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

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  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.65</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401521000056/exhibit10_81.htm"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Side Letter dated December 31, </span>2020<span style="text-decoration: underline;"> to the New Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc. dated April 19,
                  2018</span></span></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2020 and incorporated herein by
              reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.66</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000045/exhibit10_67.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Factor B Development Collaboration, Option and License Agreement by and among the Registrant, F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc., dated October 9, 2018,</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2018 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the
              SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.67</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000148/ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">First Amendment dated July 8, 2022 to Factor B Development, Collaboration, Option and License Agreement by and between the Registrant, F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, dated October 9, 2018, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2022. Portions of this exhibit have been omitted because they are
              both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.68</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000045/exhibit10_68.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Second Amended and Restated Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc., dated October 17, 2018</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2018 and incorporated herein by reference. Portions of this exhibit have been omitted
              and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.69</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036117009823/exhibit10_61.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Letter Agreement between the Registrant and Biogen MA Inc. dated October 28, 2016</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on
              Form 10-K for the year ended December 31, 2016 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.70</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036119014492/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No. 1 to Second Amended and Restated Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc., dated May 2, 2019</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2019 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.71</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000209/ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaboration and License Agreement by and between the Registrant and Novartis Pharma AG dated as of August 2, 2023</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an
            exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Portions of this exhibit have
              been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.72</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000209/ex10-3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, Development, and License Agreement by and among the Registrant, F. Hoffmann-La Roche Ltd., and Hoffmann-La Roche Inc. dated as of September 26, 2023</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.73</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401520000115/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Side Letter dated June 11, 2020 to the Second Amended and Restated Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc. dated October
              17, 2018</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and incorporated herein by reference.
              Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.74</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401521000166/ex10-2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaboration and License Agreement by and between the Registrant and BicycleTX Limited dated July 9, 2021</a>, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2021
            and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the type that the Registrant treats
              as private or confidential</span>.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.75</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000079/exhibit10-83.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No. 1 dated December 17, 2021 to the Collaboration and License Agreement by and between the Registrant and BicycleTX Limited dated July 9, 2021</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2021 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.
              Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.76</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000168/ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No. 2 dated July 28, 2022 to the Collaboration and License Agreement by and between the Registrant and BicycleTx Limited dated July 9, 2021</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2022 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.
              Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.77</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000186/ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No. 3 dated April 27, 2023 to the Collaboration and License Agreement by and between the Registrant and BicycleTx Limited dated July 9, 2021</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2023 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.
              Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>


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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

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  <div><a id="_Hlk186622894"><!--Anchor--></a></div>
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.78</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401521000166/ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amended and Restated Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc. dated July 12, 2021</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2021 and incorporated herein by reference. Portions of this exhibit have been omitted because they
              are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.79</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000079/exhibit10-84.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaboration and License Agreement by and between Akcea Therapeutics, Inc. and AstraZeneca AB dated December 6, 2021</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an
            exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2021 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.&#160; Portions of this exhibit have been
              omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.80</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000186/ex10-3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Letter Agreement dated June 29, 2023 in reference to the Collaboration and License Agreement dated December 6, 2021 by and between Akcea Therapeutics, Inc. and AstraZeneca AB</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2023 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.81</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-80.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaboration and License Agreement between the Registrant and Metagenomi, Inc. dated November 10, 2022</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the
              Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2022 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats
              as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.82</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-81.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty Purchase Agreement by and between the Registrant, Akcea Therapeutics, Inc. and Royalty Pharma Investments 2019 ICAV dated as of January 9, 2023</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2022 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii)
              the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.83</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401524000187/ex10-2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amended and Restated License Agreement by and between the Registrant and Otsuka Pharmaceutical Co., Ltd. dated June 18, 2024</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an
              exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the
              Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="exhibit19.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19</a></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Registrant&#8217;s<span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>Insider Trading Policy.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.1</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401524000116/exhibit21-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">List of Subsidiaries for the Registrant</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December
            31, 2023 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="exhibit23-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23.1</a></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consent of Independent Registered Public Accounting Firm.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#POWEROFATTORNEY" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.1</a></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Power of Attorney &#8211; Included on the signature page of this Annual Report on Form 10-K.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="exhibit31-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.1</a></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification by Chief Executive Officer Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="exhibit31-2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.2</a></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification by Chief Financial Officer Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="exhibit32-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32.1</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">+</span></div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">97</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401524000116/exhibit97.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Registrant&#8217;s Amended and Restated Clawback Policy</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended
              December 31, 2023 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following financial statements from the Ionis Pharmaceuticals, Inc. Annual Report on Form 10-K for the year ended December 31, 2024, formatted in Extensive Business Reporting Language (XBRL): (i) consolidated balance sheets, (ii) consolidated statements of operations,
            (iii) consolidated statements of comprehensive income (loss), (iv) consolidated statements of stockholders&#8217; equity (v) consolidated statements of cash flows, and (vi) notes to consolidated financial statements (detail tagged).</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10.71%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104</div>
        </td>

    <td style="width: 2.13%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 87.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cover Page Interactive Data File (formatted in iXBRL and included in exhibit 101).</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicates management compensatory plans and arrangements as required to be filed as exhibits to this Report pursuant to Item 14(c).</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">+</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">This certification is deemed not filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liability of that
            section, nor shall it be deemed incorporated by reference into any filing under the Securities Act of 133, as amended, or the Securities Exchange Act of 1934, as amended.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

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  </div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Signatures"><!--Anchor--></a>SIGNATURES</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the Registrant has duly caused this report on
    Form 10-K to be signed on its behalf by the undersigned, thereunto duly authorized on the 19<sup>th</sup> day of February, 2025.</div>

  <div style="text-align: center;"><br/>
  </div>

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  <tr>

    <td style="width: 49.81%; vertical-align: top;">&#160;</td>

    <td colspan="2" style="width: 50.19%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">IONIS PHARMACEUTICALS, INC.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 49.81%; vertical-align: top;">&#160;</td>

    <td style="width: 4.63%; vertical-align: top;">&#160;</td>

    <td style="width: 45.56%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 49.81%; vertical-align: top;">&#160;</td>

    <td style="width: 4.63%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">By:</div>
        </td>

    <td style="width: 45.56%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ BRETT P. MONIA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 49.81%; vertical-align: top;">&#160;</td>

    <td style="width: 4.63%; vertical-align: top;">&#160;</td>

    <td style="width: 45.56%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia, Ph.D.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 49.81%; vertical-align: top;">&#160;</td>

    <td style="width: 4.63%; vertical-align: top;">&#160;</td>

    <td style="width: 45.56%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Executive Officer (Principal executive officer)</div>
        </td>

  </tr>


</table>
  <div style="text-align: center;"><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="POWEROFATTORNEY"><!--Anchor--></a>POWER OF ATTORNEY</div>

  <div style="text-align: center;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">KNOW ALL MEN BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Brett P. Monia and Elizabeth L.
    Hougen, or any of them, his or her attorney-in-fact, each with the power of substitution, for him or her in any and all capacities, to sign any amendments to this Report, and to file the same, with exhibits thereto and other documents in connection
    therewith, with the Securities and Exchange Commission, hereby ratifying and confirming all that each of said attorneys-in-fact, or his or her substitute or substitutes, may do or cause to be done by virtue hereof.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf
    of the Registrant and in the capacities and on the dates indicated.</div>

  <div style="text-align: left;"><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Signatures</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Date</div>
        </td>

  </tr>

  <tr>

    <td style="width: 30.39%; vertical-align: top;">&#160;</td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">&#160;</td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ BRETT P. MONIA</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director and Chief Executive Officer</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>
        </td>

  </tr>

  <tr>

    <td style="width: 30.39%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia, Ph.D.</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Principal executive officer)</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 30.39%; vertical-align: top;">&#160;</td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">&#160;</td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ELIZABETH L. HOUGEN</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Finance and Chief Financial Officer</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>
        </td>

  </tr>

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    <td style="width: 30.39%; vertical-align: top;">
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Joseph Loscalzo, M.D., Ph.D.</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ SPENCER R. BERTHELSEN</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Spencer R. Berthelsen, M.D.</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ALLENE M. DIAZ</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Allene M. Diaz</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ MICHAEL HAYDEN</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Michael Hayden, CM OBC MB ChB PhD FRCP(C) FRSC</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ JOAN E. HERMAN</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Joan E. Herman</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ JOSEPH KLEIN</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Joseph Klein, III</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ B. LYNNE PARSHALL</div>
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    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">B. Lynne Parshall, J.D.</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ JOSEPH H. WENDER</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Joseph H. Wender</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ MICHAEL YANG</div>
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    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Michael Yang</div>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83</div>

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  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><!--PROfilePageNumberReset%Num%1%%%--></div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">INDEX TO CONSOLIDATED FINANCIAL STATEMENTS</div>

  <div style="text-align: center;"><br/>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Page</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="#AuditReport" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Report of Independent Registered Public Accounting Firm</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (PCAOB ID <span style="-sec-ix-hidden:Fact_14c6e2f0badc4c559ea9b56e518f3ff0">42</span>)</span></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-2</div>
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    <td style="width: 93.34%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="#BalanceSheet" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consolidated Balance Sheets</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> at December 31, 2024 and 2023</span></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-4</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="#IncomeStatement" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consolidated Statements of Operations</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the years ended December 31, 2024, 2023 and 2022</span></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-5</div>
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    <td style="width: 93.34%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="#ComprehensiveIncome" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consolidated Statements of Comprehensive Loss</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the years ended December 31, 2024, 2023 and 2022</span></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-6</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="#Equity" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consolidated Statements of Stockholders&#8217; Equity</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the years ended December 31, 2024, 2023 and 2022</span></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-7</div>
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    <td style="width: 93.34%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="#CashFlows" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consolidated Statements of Cash Flows</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the years ended December 31, 2024, 2023 and 2022</span></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-8</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="#Notes" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Notes to the Consolidated Financial Statements</a></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-9</div>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-1</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="AuditReport"><!--Anchor--></a>REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM</div>

  <div><br/>
  </div>

  <div style="text-align: center;"><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To the Stockholders and the Board of Directors of Ionis Pharmaceuticals, Inc.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Opinion on the Financial Statements</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have audited the accompanying consolidated balance sheets of Ionis Pharmaceuticals, Inc. (the Company) as of December 31, 2024 and 2023, the related
    consolidated statements of operations, comprehensive loss, stockholders&#8217; equity and cash flows for each of the three years in the period ended December 31, 2024, and the related notes (collectively referred to as the &#8220;consolidated financial
    statements&#8221;). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company at December 31, 2024 and 2023, and the results of its operations and its cash flows for each of the
    three years in the period ended December 31, 2024, in conformity with U.S. generally accepted accounting principles.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the Company&#8217;s internal
    control over financial reporting as of December 31, 2024, based on criteria established in Internal Control&#8212;Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework), and our report dated
    February 19, 2025 expressed an unqualified opinion thereon.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis for Opinion</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These financial statements are the responsibility of the Company&#8217;s management. Our responsibility is to express an opinion on the Company&#8217;s financial
    statements based on our audits. We are a public accounting firm registered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the
    Securities and Exchange Commission and the PCAOB.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable
    assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error
    or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also included evaluating the accounting
    principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Critical Audit Matter</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The critical audit matter communicated below is a matter arising from the current period audit of the financial statements that was communicated or required
    to be communicated to the audit committee and that: (1) relates to accounts or disclosures that are material to the financial statements and (2) involved our especially challenging, subjective or complex judgments. The communication of the critical
    audit matter does not alter in any way our opinion on the consolidated financial statements, taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on the
    accounts or disclosures to which it relates.</div>

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    </div>

  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 15.42%; vertical-align: top;">&#160;</td>

    <td style="width: 2.85%; vertical-align: top;">&#160;</td>

    <td style="width: 81.74%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Estimated Liability for Clinical Development Costs</div>
          <div>&#160;</div>
        </td>

  </tr>

  <tr>

    <td style="width: 15.42%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Description of the Matter</div>
        </td>

    <td style="width: 2.85%; vertical-align: top;">&#160;</td>

    <td style="width: 81.74%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024, the Company accrued $77.4 million for clinical development expenses. As discussed in Note 1 to the consolidated financial
            statements, the Company records costs for clinical trial activities based upon estimates of costs incurred through the balance sheet date that have yet to be invoiced related to third-party clinical management costs, laboratory and analysis
            costs, toxicology studies and investigator grants. The Company estimates its liability using assumptions about study and patient activities and the related expected expenses for those activities based on the contracted fees with service
            providers.</div>
          <div>&#160;</div>
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Auditing the Company&#8217;s accruals for clinical and contract research organization costs is especially complex as the information necessary to estimate
            the accruals is accumulated from multiple sources. In addition, in certain circumstances, the determination of the nature and level of services that have been received during the reporting period requires judgment because the timing and pattern
            of vendor invoicing does not correspond to the level of services provided and there may be delays in invoicing from vendors.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

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    <td style="width: 15%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">How We Addressed the Matter in Our Audit</div>
        </td>

    <td style="width: 3.27%; vertical-align: top;">&#160;</td>

    <td style="width: 81.73%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We obtained an understanding and evaluated the design and tested the operating effectiveness of controls over the accounting for accrued clinical
            development expenses. This included controls over management&#8217;s assessment of the assumptions and accuracy of data underlying the accrued clinical development expenses estimate.</div>
          <div>&#160;</div>
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To test the accuracy of the Company&#8217;s accrued clinical development expenses, we performed audit procedures that included, among other procedures,
            obtaining supporting evidence of the research and development activities performed for significant clinical trials and confirming with a sample of vendors the progress of activities under research and development contracts at period end. We
            corroborated the status of significant clinical development expenses through meetings with accounting and clinical project managers. We compared the costs for a sample of transactions against the related invoices and contracts, and examined a
            sample of subsequent payments to evaluate the accuracy of the accrued clinical development expenses and compared the results to the current year accrual.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ <ix:nonNumeric name="dei:AuditorName" id="Fact_4f70d4e1631540058ba326a9cce66097" contextRef="c20240101to20241231">Ernst &amp; Young LLP</ix:nonNumeric></div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have served as the Company&#8217;s auditor since 1989.</div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:AuditorLocation" id="Fact_2e0ee936a1f14e77b9ee049d8727d218" contextRef="c20240101to20241231">San Diego, California</ix:nonNumeric></div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div>

  <div><br/>
  </div>

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    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="BalanceSheet"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONSOLIDATED BALANCE SHEETS</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands, except share and par value data)</div>

  <div><br/>
  </div>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: center; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASSETS</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current assets:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash and cash equivalents</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsAtCarryingValue" id="Fact_7d7f77575df24801aeb6d430b5e2aea9" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">399,266</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Short-term investments</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShortTermInvestments" id="Fact_a1df8a4ae5fb4f9d95e154d2c09e0e03" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,931,935</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Contracts receivable</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerAssetNetCurrent" id="Fact_09ccd7c4554b495cb3b69ab0dd4c6353" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">92,188</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerAssetNetCurrent" id="Fact_264161db8a37477daa1cb9fc9575e8fb" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">97,778</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Inventories</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other current assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deposits and other assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_e7755fa54d8645189ca7a38afb274c32" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,003,675</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_bbc96043d6b84ad0a64609e7e45001dd" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,990,072</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: center; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">LIABILITIES AND
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current liabilities:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounts payable</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccountsPayableCurrent" id="Fact_d2f4209896534c34b236247e2f014047" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">42,964</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccountsPayableCurrent" id="Fact_4a77a0a95bc24ec9879730f3c54c5767" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">26,027</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued compensation</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_6757e467d4ca4989a92e1b0146882726" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">69,614</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_e13f67f862ed4bf9b0ccd8241eabef36" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">67,727</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_70b781ca48864bb9b31bb2272f1c75fd" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">108,438</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_969294300c9b472f89e106ba0b60bd69" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">147,894</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes payable</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedIncomeTaxesCurrent" id="Fact_0ac97222f6364543b31753077f08b8f9" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">34</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedIncomeTaxesCurrent" id="Fact_924182cca560478288901c6e2b93dbec" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,151</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2d12bb6f256d41509009bc5bd3a0c195" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_75004fb19a054dbb96df3227e79bee4c" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction> percent</span>
            convertible senior notes, net</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtCurrent" id="Fact_53e0bd8096d1400b91420634c1176d05" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other current liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term deferred contract revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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            convertible senior notes, net</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtNoncurrent" id="Fact_7d16c92292564b2da8688629df93896f" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">565,026</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtNoncurrent" id="Fact_6a45bae12acd45d388faff32181d6045" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">562,285</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ae9dd0da53e84dbf8340a62ff383a364" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_690ac053752949ef83ff3483789bf494" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction> percent</span>
            convertible senior notes, net</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtNoncurrent" id="Fact_650338a147284507b3de78e599e965c3" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">628,535</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtNoncurrent" id="Fact_9dbda525a6ca4d9286888b5f137d3a36" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">625,380</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties, net</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet" id="Fact_0f8401eb1c534ceb8c5e787ed3474182" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">542,212</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet" id="Fact_29c0a4d587ae4a6580341b7e52d3a582" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">513,736</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term lease liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseLiabilityNoncurrent" id="Fact_8ff8e3dd4c0843b3b44c6f4288a8d906" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">161,805</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseLiabilityNoncurrent" id="Fact_f8cdaa06d800486e87ee4eb7e792c2dc" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">170,875</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term obligations</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermLoansFromBank" id="Fact_d0bdde965a494bd1967c669121c18b69" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">51,924</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermLoansFromBank" id="Fact_b1093c295a3e4d8980c112cd144aa095" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">41,836</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Liabilities" id="Fact_72e72fa97a344884ae45c7d1457d4c58" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,415,324</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Liabilities" id="Fact_e80cd271efab4a4c8c3d5beb70de894b" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,603,386</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stockholders&#8217; equity:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated other comprehensive loss</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_3e9ce1fe826144aea3422b89b11598b2" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,645</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders&#8217; equity</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_05294b8f30334228880f67edf83e2f36" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">386,686</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total liabilities and stockholders&#8217; equity</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesAndStockholdersEquity" id="Fact_801588c240bd4ed6bb876453863968da" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,003,675</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesAndStockholdersEquity" id="Fact_52b3ab3e91024ab988399c759f32bda8" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,990,072</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-4</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="IncomeStatement"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONSOLIDATED STATEMENTS OF OPERATIONS</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands, except for per share amounts)</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 8.85pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fdaf4e7de3e14bc88036b45f358b0bc2" contextRef="c20240101to20241231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">216,090</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7043d15f95394ffe96f0662fa9fad2fa" contextRef="c20230101to20231231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">240,379</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ac6e240eca5848d5badb78f0ca60c1a3" contextRef="c20220101to20221231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">242,314</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: 8.85pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c6d2dc2fc551474d924c9b886e5a3548" contextRef="c20230101to20231231_ProductOrServiceAxis_WainusRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_90cdad5a8bca423f8a03578cc2655d3e" contextRef="c20220101to20221231_ProductOrServiceAxis_WainusRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 8.85pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other commercial revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2383678941074355b9d4925186d90ab3" contextRef="c20240101to20241231_ProductOrServiceAxis_OtherCommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">56,779</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_996fb45aa67445ee9671efa9e0f75169" contextRef="c20230101to20231231_ProductOrServiceAxis_OtherCommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">68,212</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_543c70da466649fab328153c0cb49da9" contextRef="c20220101to20221231_ProductOrServiceAxis_OtherCommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,044</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: 17.75pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fd9bb6ab6005461abb18649530165b23" contextRef="c20240101to20241231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">293,076</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_22602d3c8dbb4cce84585819b2a51d20" contextRef="c20230101to20231231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">308,591</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_00a0f7dfe1fe42f2a3f0f34b4024aee6" contextRef="c20220101to20221231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">303,358</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development revenue:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_1620967f6acc42749745d5ae96e21c91" contextRef="c20240101to20241231_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">332,647</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0b96d8115fb4483dbc8311aafd1be7ec" contextRef="c20230101to20231231_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">352,657</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e3059784aae44cb6910ec96b251c7c0c" contextRef="c20220101to20221231_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">207,222</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA joint development revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5c8de2bd919f4591baa9a3fd8807bffa" contextRef="c20240101to20241231_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">79,415</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6cc8f959f1a84a3882c5922b1c402e36" contextRef="c20230101to20231231_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">126,399</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5fa9a425ee1840dfbd98ea8bde289a33" contextRef="c20220101to20221231_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">76,787</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: 18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_98715a1d07f649c3838b9f140c95b5ed" contextRef="c20240101to20241231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">412,062</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2cf6fc29b4ae47358cac42657a6e869e" contextRef="c20230101to20231231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">479,056</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7efcdc0bff8d4b0388346f3e3a31b8c0" contextRef="c20220101to20221231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">284,009</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_00980b8be4a74f4fbdcc3edafc17198f" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">705,138</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss from operations</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_a29afc3ae1f74d74a4369f8ed00932b6" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">475,081</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_a89db9808ad84853b7f4af5bb8f658a1" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">353,730</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestExpense" id="Fact_47eb0551e96b4a789a0b721ce64eef0f" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,994</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestExpense" id="Fact_6c26daacbb594ef5a5eafb7e6d90e3cb" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,660</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_79795cca858d44bf9654f0863fef96cb" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">73,457</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_d985916eae984cf3a7294c6311bc4d0e" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss on investments</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:GainLossOnInvestments" id="Fact_2b94d6c062f44b1b9bbbf9a624ec44b8" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,889</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:GainLossOnInvestments" id="Fact_a4bee18133df49ecbd27f0eeddf96f52" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,914</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:GainLossOnInvestments" id="Fact_01d3af2113e44c429d8346d1b144f3ef" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">7,333</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gain (loss) on sale of real estate assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:GainLossOnDispositionOfAssets1" id="Fact_c3a4479d5bc24c12bbb3654f2b59fba2" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">12</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:GainLossOnDispositionOfAssets1" id="Fact_1e981ccfec9e4e77bdb93b732ca6bb87" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">161</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other income (expense)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherNonoperatingIncomeExpense" id="Fact_516792b864244fea81a047aaeb6a86f7" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,343</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherNonoperatingIncomeExpense" id="Fact_df31a318f46e40c0bad155f92c7bffb9" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,256</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherNonoperatingIncomeExpense" id="Fact_95a44b06b165497c90c92f0ecb837d5d" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">7,274</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss before income tax benefit (expense)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_786ffe6ab1c44b428a4fc9133fa1fb21" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">460,068</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_d3bdd0f2404d4109ab52a26b4122517d" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">333,965</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_abea68078429482298990eda2a273682" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">257,985</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income tax benefit (expense)</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_25eb94c1a44848a4ae8038f050bdb154" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">6,171</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_5b1c8e20abb84c34b626e66d15f639fe" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,321</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_4e00bc85f9de44bc9fae3e310059dd54" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_eed2832b2f23443a8a7b6a11b3b5c8be" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">453,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_17fba83bb5c645feab5192b45331713f" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">366,286</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_1b16a95e7fa948b78f84194e8da4f693" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic and diluted net loss per share</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_f5d991f3a037439da834811b6b2c9680" contextRef="c20240101to20241231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_ad4c690aa177438c98b7e63bbcd61da7" contextRef="c20240101to20241231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">3.04</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_7cdec1311ca947dfbacb3efc23b5ef61" contextRef="c20230101to20231231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_2c847af7934d4aee8d1e75c8c45eaaed" contextRef="c20230101to20231231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">2.56</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_f8c8aa80739c448c87fb108a521d3b50" contextRef="c20220101to20221231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_dc69ad9fdaac456cb95135c896add9e4" contextRef="c20220101to20221231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">1.90</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares used in computing basic and diluted net loss per share</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_240816d0c41d4bb8946ce32d9ec238f1" contextRef="c20240101to20241231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_974483869c87424686f8a9d8ad9407f8" contextRef="c20240101to20241231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">149,514</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_9344acea647e4a1f9b5346ba564f05a7" contextRef="c20230101to20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_57a007ce704b4b8e9d16bf5187758b1a" contextRef="c20230101to20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">143,190</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_7447762242904f9289b584753a2591b0" contextRef="c20220101to20221231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_24585fd306204e04ac047eefaae344a7" contextRef="c20220101to20221231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">141,848</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-5</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="ComprehensiveIncome"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands)</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_ca9d6b6e811d4d90a3511939ceaffd35" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">453,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_0f152c7175c442d096186ccdac7163b8" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">366,286</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_e9347ab362a94c8f9fec26b2321644a8" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized gains (losses) on investments, net of tax</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_33ff3ee28c9b4c45b1a904711a9fffdb" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,107</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_7ada2fcd89584f6e9d084b26c02bad37" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">24,484</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_48783ec4c4a4439782c377df7893c03c" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24,395</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Currency translation adjustment</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_0118d01a0fc0483d942b9e51407b4717" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">273</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_e0cf23c629544136a3b19d99634a49a6" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">351</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_107faab7668f4901940b3c076c0c0ec6" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">417</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Comprehensive loss</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_88990aa910f44465b514db16de1b6797" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">452,063</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_a94a014398884db3aad264a9afa0f0b9" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">341,451</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_952a61bbba0241e4b821f51c3f0cbaf0" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">294,534</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-6</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Equity"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">CONSOLIDATED STATEMENTS OF STOCKHOLDERS</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> EQUITY</span></div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands)</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Common Stock</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Additional</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated Other</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Ionis</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Stockholders</span>&#8217;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Paid in Capital</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Comprehensive Loss</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deficit</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Equity</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at December 31, <span style="text-indent: 0pt;">2021</span></div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_e117c0623dcf44afaffde41830ff31f2" contextRef="c20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">141,210</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_c2ee42f06fe64835a05ef7841d2d5bee" contextRef="c20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">141</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_61b12d938cc04bbd933859666c726023" contextRef="c20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,964,167</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_761affc8eaf842578c2a954083f3e28b" contextRef="c20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,668</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_7ce172fc43e84fe9a84cda9a4771f340" contextRef="c20211231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,159,903</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_d7625d3c6da54d3c8303ca9e6db6c22e" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">771,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_b699b94c66764330a7a4dd60cfe07928" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_031beff8601a4b50b1c41faf88b4db91" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_2c8cd11420aa41ba8dbf194cc8c306a6" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_ea199b5eabb5480b9369c6725c638c86" contextRef="c20220101to20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_4b17e4c7ddb948378b5dc3b978592c2a" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized losses, net of tax</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_75d5b0ba5ab74db081164c7c0d5bef1d" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_5516c0cfbea4489cb3f64b2e9a7d1954" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_43ff86faa9754d818d96b4bcf1662d56" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24,395</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_1b81d231e08446d5be7fc2b7840d9fee" contextRef="c20220101to20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_bfbc1b2a123a4b6e84f6bf54825f5acd" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24,395</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign currency translation</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_50a37a75aedf40108038ac8776d5bc2a" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_f62caf56819e4811a0cc6f9ace6f821e" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_6d18a3332dab43f59a21c8d2f1489a27" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">417</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_60d6221293b84c1ea84609e2a699912c" contextRef="c20220101to20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_0c6ad3fa4d9d49368f4ce867b5152ed7" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">417</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of common stock in connection with employee stock plans, net</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_acdf70a2832b43b187cc28260d07701f" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_d53119298ae5494a8a29986a67a7b5ac" contextRef="c20220101to20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_36d702b809b6438bb9992520363072bc" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,373</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_16b471403f9c439e97677ad055ba8ea5" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_7df4cacc691c494eb7abbee279bf828b" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">100,264</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_e83c73ef6e1a48cdab01607508691d45" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_473acb72b50d46e2912b68388715952b" contextRef="c20220101to20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_48fe59c7a1864cbb84ddefd32b4f681e" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">100,264</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation" id="Fact_0e67bea4443f4bae9cd5edccf41111cf" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">346</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_f50b55d8ef9e493a980de223ce83bd7e" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_b40696a2aa1a463aa588302783bc1c6e" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,953</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_aa8b717f16a8434fa7369d0393962f2b" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_2a82343fb6bd448db961d1d4323f0b11" contextRef="c20220101to20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_fcc84a575d9e4bd697d6f06df79559df" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,953</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at December 31, <span style="text-indent: 0pt;">2022</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_60e0ac539c624466a7e961a5cda44d3a" contextRef="c20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">142,058</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_4b39284014b0418f90e000374da7580f" contextRef="c20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">142</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_6585fe6638524b79b937ab63b9db5d75" contextRef="c20221231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,059,850</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_d286f9a454bc438c8afed1012262b3ab" contextRef="c20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">57,480</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_2ff016c0f0f747c19ebd4bac48864260" contextRef="c20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,429,625</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized gains, net of tax</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_f70df17298104bb29ef7861c6b585f0e" contextRef="c20230101to20231231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_6fb19bacbb7d415481e528316894c7ee" contextRef="c20230101to20231231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_50d79b4af6c14ee1864560317e9c1c75" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">24,484</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign currency translation</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_4cbf169782bc4f10bde4c3ae85dc7111" contextRef="c20230101to20231231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_333a9818653b4dfaab93cbf0c5a77aaa" contextRef="c20230101to20231231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_49356eab4b864e50ae114d9ec765e817" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">351</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of common stock in connection with employee stock plans, net</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_b764cf722c1a4373ba116f7331963b6e" contextRef="c20230101to20231231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,439</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_e0f954339b0b486b8eb0622218c8430b" contextRef="c20230101to20231231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_f1f39c8f1962432e8fd6b5b78bfe0cf1" contextRef="c20230101to20231231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_ab997a8b7d4a4042ab48b4f20127f6b2" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,441</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_4769b7f8ea594366a73ab91db2a60fa9" contextRef="c20230101to20231231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3719dc6e9f1b486dae7106b08772f201" contextRef="c20230101to20231231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_49a44ab58d2d49f8b1053aca4e966011" contextRef="c20230101to20231231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_dc61a61ec6984fbb83f9646ef7ebb30f" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">105,809</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at December 31, <span style="text-indent: 0pt;">2023</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_dcb079e20cba446096baf2d275d36dd5" contextRef="c20231231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">144,341</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_d01227787819409c840436d67e7d48a3" contextRef="c20231231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">144</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_acc570beab1c44b1b82a54a05d599805" contextRef="c20231231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,215,098</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_23b29f4e087c4f1ca664c32300610294" contextRef="c20231231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,645</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_71c821501e124dbfa12ced3159be86a4" contextRef="c20231231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,795,911</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_b1711f8987654d248ea55f4d0db1c024" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">386,686</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_833dc2d79f584f5cadd8fbb8afa29236" contextRef="c20240101to20241231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_688bec339ca64d21a9b56fd99f2a667e" contextRef="c20240101to20241231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_2c0f61fe913a4e9c87a2ecd4f94a7897" contextRef="c20240101to20241231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_3178904620f649fd815c50c1e7ed399f" contextRef="c20240101to20241231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">453,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_f243d5703018413db94848f32ca2937c" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">453,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized gains, net of tax</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_1d4ee35e2c024559a37a84c8318f1601" contextRef="c20240101to20241231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_7d3cc28a8d714c2892f946fd7d69085f" contextRef="c20240101to20241231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_5b13464fcc914218a22621cadb3f01cf" contextRef="c20240101to20241231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,107</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_9612b70e89ab4a65902c6735833f3cf2" contextRef="c20240101to20241231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_2efba56ab30f4a1787e7e7083c0cea31" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,107</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign currency translation</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_95783d31dfff4e85b4c5c96c65e53165" contextRef="c20240101to20241231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of public common stock, net</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesNewIssues" id="Fact_8d3ab10b7e704c5a8dbe5899400bee63" contextRef="c20240101to20241231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,500</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_7988f0fa0b554b49bf2f351011560466" contextRef="c20240101to20241231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">12</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_fd2b7c8c6e9a4627a5a07891ada820fa" contextRef="c20240101to20241231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">489,108</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_4ce0064393d44c6389d87e7012f27666" contextRef="c20240101to20241231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_107d54c7857a449e8fbedb5f5102784f" contextRef="c20240101to20241231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_65fec3b007af4f1cb03ce36710769d2c" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">489,120</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3984b222032b4f89a6067a1a1115ba11" contextRef="c20240101to20241231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_aee075691688409a968dbc6bfaabb0b8" contextRef="c20240101to20241231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">130,999</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_56cd8c22ed5544bbb6a31360f46ba604" contextRef="c20240101to20241231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3058a5ae36ca41e8bec4bc5d2b8cd05a" contextRef="c20240101to20241231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3ae1822c76c04a1992dde0883ff4a37c" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">130,999</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at December 31, <span style="text-indent: 0pt;">2024</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_1d1f0719541143f2ae5ac80a19fb4007" contextRef="c20241231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">157,909</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_74064f8288c1486bb2496106d6fd8aa7" contextRef="c20241231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">158</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_41e9cc98d38a41778cf6eb70280117c2" contextRef="c20241231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,868,812</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_aced03aa44534069aacaa219a523b4fc" contextRef="c20241231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">30,811</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_05be694dedb54ba2866c147ae24a252c" contextRef="c20241231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,249,808</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_08847d93eb194cbc8441f04f28fab350" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">588,351</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>

  <div><br/>
  </div>

  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-7</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="CashFlows"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONSOLIDATED STATEMENTS OF CASH FLOWS</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands)</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating activities:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_74418700e541478eadc5aced379a124b" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">453,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_3fb9b4a0ea3c4f27a1399c4165b5801f" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">366,286</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_39b8baae321b42f7a5f4fa01fd0016cc" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to reconcile net loss to net cash used in operating activities:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Depreciation</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Depreciation" id="Fact_9783424161d0448dad5051ce77601a96" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,614</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Depreciation" id="Fact_6e647886642547db938d5dd7ac6cb6ac" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,292</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Depreciation" id="Fact_c043d99cc86a49da958b7b3be663c1e1" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,328</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of right-of-use operating lease assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense" id="Fact_187fd18217c9402ba4a18dc3da990453" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,040</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense" id="Fact_97e6d2268c574e3d8f29df4998aec6d6" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,647</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense" id="Fact_215c70afe4f549f890056ebd2c3be83f" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,362</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of other assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_c4419687fb464fe5bdc6e0d2984bef36" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,336</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of debt issuance costs</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_8299ca7b84184a219ca22bdd8885ded6" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,373</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:RoyaltyPayments" id="Fact_d47b21c305754fe0a2fd6773a9c1252f" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">44,981</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:RoyaltyPayments" id="Fact_c60012caafca46189dd4cda5dc6cdc9b" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash interest related to sale of future royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:InterestExpenseRelatedToSaleOfFutureRoyalties" id="Fact_c41fe7cf220e42039063da2980cda172" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">72,846</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:InterestExpenseRelatedToSaleOfFutureRoyalties" id="Fact_1ae0898f26224df5b04dc8b01cf671c7" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensation" id="Fact_de86964f1c204681a24953a828812433" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">130,200</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gain on early retirement of debt</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_e867493ef4ff4d3ebe904b6d5afd0509" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_746295e1c66f4d83896cdde464856584" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">13,389</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_92b9752085fc414faf69a3c81e0bfb45" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash losses related to disposal of property, plant and equipment</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss (gain) on sale of real estate assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SaleAndLeasebackTransactionGainLossNet" id="Fact_47721d4758854281803bfb89b067868b" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Contracts receivable</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerAsset" id="Fact_f68a004f44a6458192f1daa14c3a54bb" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">5,590</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerAsset" id="Fact_e61ccb4ba21a4ee397258365ed72f449" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">72,059</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerAsset" id="Fact_d476ac7c7da448f6a23a134d6afa1da6" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">36,358</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Inventories</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInInventories" id="Fact_085c28a5897b4fdc902bd3eb96b38cfe" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,071</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInInventories" id="Fact_721b959345b1466b92ba324d3da7222a" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,469</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInInventories" id="Fact_f0c18d8f1c034754aa7043aeea9887ef" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">5,326</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other current and long-term assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherOperatingAssets" id="Fact_864803efe0c94dcc8ef6304a526731c5" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,857</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherOperatingAssets" id="Fact_9c22cd95e9714742b7353b0030bbba8e" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">33,763</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherOperatingAssets" id="Fact_6e52fd98d6cb4429b89f68777b6ce49d" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,235</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounts payable</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable" id="Fact_cbe5d4f72a7b47b6bbf20a734efa0ff9" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,117</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherCurrentLiabilities" id="Fact_c2d76681eaf6401eb0820fac87914240" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">42,993</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherCurrentLiabilities" id="Fact_46fb0027cc774970b1e33fe73a8d0134" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">5,506</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred contract revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_6eed7a6f16674d629d60401fee845c19" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">156,819</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_860c87bb13ca432ab6413fcb41ab7d48" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">13,967</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_9c03c531ef514d558aa7fca25bb6b718" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">71,248</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash used in operating activities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_19c256c737ca49a4a82b43e1d4907fd7" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">500,947</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_6ac8228472434c89928ff5906d8cdfa8" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">307,513</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_39199cc3649f4be29630e4d9f60a5e3f" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">274,370</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investing activities:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchases of short-term investments</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt" id="Fact_e72b6b733f32469391537642ed9f915f" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,852,858</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt" id="Fact_dade26c6f20f4b60a4feec4e181794e8" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,770,814</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt" id="Fact_67fd6ba04f7343b8835d000a36955a72" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,485,772</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of short-term investments</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_4c7538b4bbdc45c8b0632c5597958d34" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,769,172</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_38e7752c94b34c97a1435e616eb5db40" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,584,676</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_80d5593638ef4ce1981649265ba744b9" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">989,152</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchases of property, plant and equipment</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_af7f2fbf99644b83883250b2765bc5ae" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">45,280</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_28d3f3d53dd04a84a5b65fcacb820e59" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">23,805</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_efecf5285ea845a984a8c24b6cf68305" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">254,083</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquireIntangibleAssets" id="Fact_c4ddbc47fdde42a994020ac78cea3e4d" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,061</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInInvestingActivities" id="Fact_dc86ed420ba74326be5713c12aa09032" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">214,127</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInInvestingActivities" id="Fact_25c5a36f9c66441bbadcb049e1be0f09" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">262,636</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financing activities:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_9766979c83c547faaf9db39fd1ec8b13" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">33,609</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_e8614ff277e9476fabd71fcec8d4876c" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,442</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_847a8383a3104ae19857ffdfc7350136" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,373</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from issuance of common stock in public offering, net</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfCommonStock" id="Fact_62e5d8af366b495988c8f5678e6fe2dd" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">489,120</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfCommonStock" id="Fact_96dab0dfec20413eb62d1048a318a408" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfCommonStock" id="Fact_6212dd7accbd459096529bdbc2cfb27a" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Repayment of <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f73cf330b608459aacdcc331c5e7b288" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8a357a2eda9c42d08c2f91e48837eab3" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction> percent</span> convertible senior notes</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_040600e4d3df44dfb777cdf5065c4a97" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">44,504</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_977e8461886943e5b2ffd66265968ff7" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">487,943</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_bb5e82339c6c4233bc58f3567f5b5acd" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from issuance of <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4642a52ab9ce4907b39eed0ffa26c5a5" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction> percent</span> convertible senior notes</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_7342e63e918d42e191e29bcf117f5cad" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsOfDebtIssuanceCosts" id="Fact_295ea68d59684798888a6f3e259aa649" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsOfDebtIssuanceCosts" id="Fact_e6bf4f1d9a154dc792f7ba7e5860ef4f" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,175</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsOfDebtIssuanceCosts" id="Fact_df6265ad6ec44742b960a285ededbf09" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of future royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ProceedsFromSaleOfFutureRoyalties" id="Fact_95dc46bd905b48f89195b36692463284" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ProceedsFromSaleOfFutureRoyalties" id="Fact_2cbd526918944d95bccd56b91ec7d500" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">500,000</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ProceedsFromSaleOfFutureRoyalties" id="Fact_1a1dbc0d5c5f44748accd5559b4e128b" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Payments of transaction costs related to sale of future royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_c0775a432b6c4ebbb38dcca09c33571d" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_6f9e0cfc307a413ebd3938e230788a53" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,434</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_39edc9b6eae64a328dfef179b5346bcd" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">29</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from real estate transaction</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ProceedsFromRealEstateTransaction" id="Fact_419677fa184d47dbad3d65cb9d24a606" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ProceedsFromRealEstateTransaction" id="Fact_ede17d8747da49a599d2995e53ce2a8f" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,352</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ProceedsFromRealEstateTransaction" id="Fact_ac9726081ddf4ff78ce21581fac853e2" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Principal payments on mortgage debt</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RepaymentsOfSecuredDebt" id="Fact_588ad9a9626c41d3bf5f5e384b12775c" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">167</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RepaymentsOfSecuredDebt" id="Fact_abc6a6e24b2d4210a3f01c96ac626cc1" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">160</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RepaymentsOfSecuredDebt" id="Fact_bf3b3c7f48c1498882ec15e09ed05b04" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">50,686</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_d0c63549a159422d8925dbeac4505a02" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_4420366a0a5648d6bb96c8031145c0f8" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_0355270d749349ec8d585f6e041767cc" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,953</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash provided by (used in) financing activities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInFinancingActivities" id="Fact_f60764a062974ce7927a4f93e49247af" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">478,058</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInFinancingActivities" id="Fact_8fe541f932de4397b19679cb15ea1ecb" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">644,082</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInFinancingActivities" id="Fact_5f3ea28877314458b840e3b2bce60168" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">55,295</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effects of exchange rates on cash</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_323a2b839be44267a57618d86a42c961" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">122,794</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_15eb19737eab4e538dc8c84af74c487a" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">592,719</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash and cash equivalents at beginning of year</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_07f0dd136aab4f3da006f1b408361fc2" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">399,266</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_2593d613c153433fa9848ecd8821eae6" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">276,472</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_ad3a4e4b42454d7f972b7be959dc74c6" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">869,191</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash and cash equivalents at end of year</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_3dde4ee002f342ccb3133c6d89c8a4d4" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">242,077</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_926ccf414d0f48ce937cd18166493947" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">399,266</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_033a33f533a14ef7ad9a34a1466c774e" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">276,472</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Supplemental disclosures of cash flow information:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest paid</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InterestPaidNet" id="Fact_6419ea93d02441d486308749fc3a69a2" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,869</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InterestPaidNet" id="Fact_2249909088154c1986cb1b79f68deed3" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,512</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InterestPaidNet" id="Fact_8c17d62edf1c473d8eaf535bf23b8f15" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,898</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes paid (refunds received)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxesPaidNet" id="Fact_c06db4a22c154dd4a32207c8b41d23bc" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">5,620</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxesPaidNet" id="Fact_5318aab49def4a0f8b51981f5a454d31" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">48,334</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxesPaidNet" id="Fact_368f89931f0e430083f0bf01db6da5a7" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,010</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Supplemental disclosures of non-cash investing and financing activities:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use assets obtained in exchange for lease liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" id="Fact_2e73a62ed6b94af4bbaf09f894de757d" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" id="Fact_6738abc647624c90a0e3177ac78e71ea" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" id="Fact_5c855545977c46e98693fab1376c9200" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">168,931</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts accrued for capital and patent expenditures</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:CapitalAndPatentExpendituresIncurredButNotYetPaid" id="Fact_7a2dfc2a1d1a4605b0263f1b76478acd" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">947</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:CapitalAndPatentExpendituresIncurredButNotYetPaid" id="Fact_f73d104fa14b4c6da9e22f41979ab811" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">172</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:CapitalAndPatentExpendituresIncurredButNotYetPaid" id="Fact_2e89ce6cc7c74c4aafae3dbbf97500c4" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,767</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


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  <div><br/>
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  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-8</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Notes"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">NOTES TO CONSOLIDATED FINANCIAL STATEMENTS</div>

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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1. Organization and Significant Accounting Policies</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;).</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Organization and Business Activity</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporated in California on January 10, 1989. In conjunction with our IPO, we reorganized as a Delaware corporation in April 1991. We
    were organized principally to develop human therapeutic medicines using antisense technology. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We operate as a <span style="-sec-ix-hidden:Fact_0a919095f48f42f79abafacb21f6d831">single</span> segment, Ionis
    operations, because our chief operating decision maker, or CODM, reviews operating results on an aggregate basis and manages our operations as a single operating segment. Refer to Note 12, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Information</span>, for further details on our segment information.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Use of Estimates</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the United States, or
    U.S., that require us to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue Recognition</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting
    receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include
    the amounts within deferred revenue in our consolidated balance sheets.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities
    performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC,
    Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration
      arrangements within the scope of ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that contain multiple elements, we </span>first<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
      determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC </span>606<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. When we determine elements of a collaboration do not
      reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with
    multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our WAINUA collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue; while
    we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as selling, general and administrative, or SG&amp;A, expense and research and development, or R&amp;D, expense,
    respectively.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of
    revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Identify the contract</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner or customer.</div>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-9</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
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    <td style="width: 18pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">2.</span></td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Identify the performance obligations</div>
        </td>

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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the
    contract.</div>
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<div><br/>
  </div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">3.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Determine the transaction price</div>
        </td>

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<div><br/>
  </div>
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  <div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration
      agreement, including any variable consideration.</div>
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<div><br/>
    </div>
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  </div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">4.</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Allocate the transaction price</div>
        </td>

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<div><br/>
  </div>
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  <div>
    <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a42" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a43"><ix:continuation id="Text_a77515959d2d4911a3d035bff805b90a26" continuedAt="Text_a77515959d2d4911a3d035bff805b90a27">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Next, we allocate the transaction price to each of our
        performance obligations. When we have to allocate the transaction price to more than </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligation, we make estimates of the relative stand-alone
        selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do
        not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</span></div>
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  </div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">5.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Recognize revenue</div>
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<div><br/>
  </div>
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  <div>
    <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a46" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a47"><ix:continuation id="Text_a77515959d2d4911a3d035bff805b90a30" continuedAt="Text_a77515959d2d4911a3d035bff805b90a31">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize revenue in </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ways, over time or at a point in time. We recognize revenue over time when we are executing on our
        performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a
        specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</span></div>
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<div><br/>
    </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue, which
      in certain cases may require us to estimate our royalty revenue.</div>
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  </div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Amendments to Agreements</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the
    accounting for the amendment:</div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the goods and/or services are sold at a stand-alone selling price.</div>
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<div><br/>
  </div>
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  <div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at
      a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are
      distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment
      to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a
      cumulative-effect adjustment.</div>
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  </div>
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<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Multiple agreements</span></div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to
    determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div>
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<div><br/>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the agreements were negotiated together with a single objective;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div>
        </td>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting
    guidance requires us to account for them as a combined arrangement.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative
      Arrangements and Licensing Agreements</span>, for further discussion of our 2018 neurology collaboration with Biogen that included multiple agreements which we negotiated concurrently and in contemplation of one another.</div>
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<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we
      have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts
      receivable to be unconditional. We typically receive payment within </span><ix:nonFraction name="ions:NumberOfQuartersAfterBillingWhenPaymentIsReceived" id="Fact_13d4b765faea4f21b13d4310d6749429" contextRef="c20240101to20241231" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;quarter of billing our partner or customer</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024,
    approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_10e7a43398a0499b9e7ce86d84750009" contextRef="c20240101to20241231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_ThreeSignificantCustomersMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">95.6</ix:nonFraction> percent of our contracts receivables were from <ix:nonFraction name="ions:NumberOfSignificantCustomers" id="Fact_fa43dcb0b8ee41488642917fbbe8ac66" contextRef="c20240101to20241231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> significant customers. As of December 31, 2023, approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_bb586f81c8674dd6b924c9686075aa5b" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_OneSignificantCustomerMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">87.8</ix:nonFraction> percent of our contracts receivables were from <ix:nonFraction name="ions:NumberOfSignificantCustomers" id="Fact_3f1c8550953d4fb1bbaac07917b18557" contextRef="c20230101to20231231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction>
    significant customer.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled Royalties</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our unbilled royalties represent our right to receive consideration from our partners in advance of when we are eligible to bill them for
    royalties. We include these unbilled amounts in other current assets in our consolidated balance sheets.</div>
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<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive
      payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue in our consolidated balance sheets.</span> During the years ended December 31, 2024 and 2023, we recognized $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_7a9ec3bea8ad464ca6e12c6aa16435cd" contextRef="c20240101to20241231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">166.1</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_ced6b030f6d146bb91eabbce81e6f413" contextRef="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">78.2</ix:nonFraction> million of revenue from
    amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Sales</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs
    and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Patent Expenses</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and
    manufacturing costs, patents and other expenses that are directly related to our R&amp;D operations. We expense R&amp;D costs as we incur them. When we make payments for R&amp;D services prior to the services being rendered, we record those amounts as
    prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in R&amp;D expenses are costs associated with our partner agreements. In 2024, 2023 and 2022, patent expenses were $<ix:nonFraction name="ions:PatentExpenses" id="Fact_85866a721e84472989175bb6188f4c57" contextRef="c20240101to20241231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.3</ix:nonFraction> million, $<ix:nonFraction name="ions:PatentExpenses" id="Fact_a0ff596166e44c50ba79c8d446d1bb4e" contextRef="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.3</ix:nonFraction> million and $<ix:nonFraction name="ions:PatentExpenses" id="Fact_18be9a3bed5e4b5a815b9ba827f8eb2d" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.7</ix:nonFraction> million, respectively.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities
    for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development
    credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and
    measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight
    of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit
    as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes.
    Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these
    reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the
    provision for income taxes in the period in which we make such determination.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In
    assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We
    base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from
    our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be
    realized. </div>
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  </div>
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  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a103" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a104"><ix:nonNumeric name="us-gaap:EarningsPerSharePolicyTextBlock" id="Text_47e97970a2d74b528c3d5e13d3b65bad" contextRef="c20240101to20241231" escape="true" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a41">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss per Share</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a104" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a105"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a41" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a42">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a105" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a106"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a42" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a43">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a106" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a107"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a43" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a44">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a107" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a108"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a44" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a45">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We compute basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the
    period.</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a108" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a109"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a45" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a46">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a109" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a110"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a46" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a47">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Diluted net loss per share</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a110" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a111"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a47" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a48">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a111" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a112"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a48" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a49">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024,
    2023 and 2022, we incurred a net
    loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss
    per share:</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a112" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a113"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a49" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a410">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a113" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a114"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a410" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a411">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_73bfeee93f8546f5b370edd9f616a4d4" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5c056baf11664eb8bb1412c9ff380ed0" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f51d9adf928c4a84aaf14638a3b4ce14" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction></ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_769655fa2afc4791b0ea57ec99a02fed" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_27a4ad482c384321b81448144513139e" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_45c13a6875054757a3b79a207fb51a99" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction></ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a114" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a115"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a411" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a412">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1c6dd4aa81824cad8f86c21b0cbc10a0" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8e8c26f5c9244588940e55bdaee73dca" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_270fcf1505694f01b837e6326d809bfd" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction></ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a115" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a116"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a412" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a413">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2458a3845ed24510a9f7ee91849cccfd" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_eb796a9cff164893992d0656c18cb133" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b26c82d7992442ff96c5568ee51f49f2" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction></ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f3006fbac4f149b38e6462396a20e208" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_d9312f49e9424c82bffc13bbc2944526" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6f2d97c4eb3c416a953a12543f2d88d9" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction></ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a116" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a117"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a413" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a414">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_94aea085060d41bc80cec7916b6f1fdf" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_313a82c8d6674d4c8879cbc00534b803" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1f4d9d777dda40daac28b07c65d54061" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction></ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a117" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a118"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a414" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a415">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a118" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a119"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a415" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a416">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a119" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a120"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a416" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a417">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a120" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a121"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a417" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a418">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Stock Purchase Plan, or ESPP.</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a121" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a122"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a418" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a419">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a122" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a123"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a419" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a420">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024 and 2023, common stock underlying the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_16bb52a29f0c4c09b041362635a81023" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_d78308e8178f4c7fb2b6e0190ad9d696" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction></ix:nonFraction> percent convertible senior notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f6cbce7782c24a39bbae59169e6d3d51" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes, would also
    have had an anti-dilutive effect on net loss per share.</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_fedc8da5ca594cc98e28e74dad653e4a123" continuedAt="Text_fedc8da5ca594cc98e28e74dad653e4a124"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a420" continuedAt="Text_caf9f0a480b940e8b76566a6b5e7a0a421">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:continuation id="Text_caf9f0a480b940e8b76566a6b5e7a0a421"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">As of December 31, 2024, 2023 and 2022, we had outstanding warrants related to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ba5cb56662c545889373089bf19108a7" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_73a6a70d21a742afababa9d39679ccb0" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_25c44309c95c4d44bd80b4061a6f7df3" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction></ix:nonFraction>% Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c70e1c3405324e9a9775523fd3e3866f" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_bd13f09db3d54fbbbdaf98adb97cd598" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5607593758b2425c96658da021cfddf2" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction></ix:nonFraction>% Notes. We will include the shares issuable
    under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</span></ix:continuation> During 2024, 2023 and 2022, the market price
    of our common stock did not exceed the strike price of the warrants.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-Based Compensation Expense</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock
    purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service
    period in our consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated
    multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award
    were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Stock Options and Stock Purchase Rights:</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant
    date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the
    awards, and actual and projected employee stock option exercise behaviors. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted
    based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options
    granted under these plans from <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_b4d09574c5df412aa2e3ca9444baf598" contextRef="c20240101to20241231_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_7790526b5c3648779a4130225f212db9" contextRef="c20240101to20241231_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" format="ixt-sec:durwordsen">ten years</ix:nonNumeric> for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this
    change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the years ended December 31, 2024, 2023 and 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we
    gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RSU&#8217;s:</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest
    annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_9c07a9a996a942cfa5196c4e73d65a5f" contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_a9d4677fe482460496896805b6e948d8" contextRef="c20240101to20241231_AwardDateAxis_GrantedPriorToJune2020Member_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorsMember" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. The annual RSUs we granted to our board of directors after June 2020 fully vest after <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_317dd58aff2644f5948252ec0ede060a" contextRef="c20240101to20241231_AwardDateAxis_GrantedAfterJune2020Member_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorsMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric>. The RSUs we granted to board members at their initial appointment to the board of directors vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_cc8fbd3efd6d4225988931e46abd4016" contextRef="c20240101to20241231_AwardDateAxis_GrantedAtInitialAppointmentMember_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorsMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric> period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PRSU&#8217;s:</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added
    PRSU awards to the compensation for our other Section 16 officers. Under the terms of the PRSUs we granted in 2020 through 2022, <span style="-sec-ix-hidden:Fact_65d15117ab79462e81dfb8bbb86a0107"><span style="-sec-ix-hidden:Fact_e9934b85c6af480197be8d0d8b5ea434"><span style="-sec-ix-hidden:Fact_5599af32346c4fce91fa6d27caf4b474">one third</span></span></span>
    of the PRSUs may vest at the end of <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" id="Fact_4556558cf7c146f081140dde2cf15e02" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> separate performance periods spread over the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_9ee4b8f0d0fc415d8fedacb7e025157a" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" format="ixt-sec:durwordsen">three years</ix:nonNumeric> following the date of grant (i.e., the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_4a3b1878ccda46faa7e3dcc5b7ecf3f1" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" format="ixt-sec:durwordsen">one-year</ix:nonNumeric> period
    commencing on the date of grant and ending on the first anniversary of the date of grant; the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_10bf9fa3aeef4afaa6e49f9def9210ca" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheTwoMember" format="ixt-sec:durwordsen">two-year</ix:nonNumeric> period commencing on the date of grant
    and ending on the second anniversary of the date of grant; and the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_cb84749fad7546409795da36a9b7b020" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheThreeMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric> period commencing on the date of grant and ending on the third
    anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" id="Fact_b8fc319755bc4ee498c93684446fe058" contextRef="c20240101to20241231_AwardDateAxis_Granted2020Through2022Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U002" decimals="0" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_b0b7848e22764764b4bcbddd5a2927ff" contextRef="c20240101to20241231_AwardDateAxis_Granted2020Through2022Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MinimumMember" unitRef="U003" decimals="INF" scale="0" format="ixt-sec:numwordsen">zero</ix:nonFraction> to <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_1370c49d2caf4b69b350f951933b5194" contextRef="c20240101to20241231_AwardDateAxis_Granted2020Through2022Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">150</ix:nonFraction> percent of the target number
    depending on our relative TSR. These PRSU awards also included an alternative <ix:nonNumeric name="ions:TermOfAlternativePayoutMechanism" id="Fact_fdf8d7ca12a54802a6d105e91ca3499f" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric> payout mechanism, or the Alternative Calculation, under
    which we must calculate an alternative payout at the end of the final <ix:nonNumeric name="ions:MeasurementPeriodForAlternativePayoutMechanism" id="Fact_636cbb73122d4a6f801622ea77774c32" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric> measurement period assuming the only measurement period for all
    shares under the award was the <ix:nonNumeric name="ions:MeasurementPeriodForAlternativePayoutMechanism" id="Fact_61e2f6c38e124a9bbf993e2175105896" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric> period. If the Alternative Calculation is greater than payouts under the sum of the <ix:nonNumeric name="ions:MeasurementPeriodForAlternativePayoutMechanism" id="Fact_c56a304476f24fa4ae572f8c62dbc6be" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:durwordsen">three years</ix:nonNumeric>, then such PRSU award will pay out to achieve the number of shares payable under the Alternative Calculation.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the PRSUs we granted in 2024 and 2023, <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_5c153f144c1b492e8ca12ea3a0e6b759" contextRef="c20240101to20241231_AwardDateAxis_GrantedIn2024And2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction> percent of the PRSUs may vest at the end of the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_8d3cd9d9420b469fa8ebee749aed8aa9" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric> performance period based on our relative TSR as
    compared to a peer group of companies and as measured at the end of the performance period. Under the terms of the grants, <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" id="Fact_a77aae45c4ef4362ac6ed7f43a02f281" contextRef="c20240101to20241231_AwardDateAxis_GrantedIn2024And2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U002" decimals="0" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> number of PRSUs is
    guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_cef441d443044be391448d0eecd8a2b3" contextRef="c20240101to20241231_AwardDateAxis_GrantedIn2024And2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MinimumMember" unitRef="U003" decimals="INF" scale="0" format="ixt-sec:numwordsen">zero</ix:nonFraction> to <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_c5042a913c244bf085af7da30aab1dff" contextRef="c20240101to20241231_AwardDateAxis_GrantedIn2024And2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">200</ix:nonFraction> percent of the target number depending on our relative TSR.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which
    represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Note 8, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Stockholders&#8217; Equity,</span>
    for additional information regarding our stock-based compensation plans.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Concentration of Credit Risk</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term
    investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions,
    corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#8217;s, Standard &amp; Poor&#8217;s, or S&amp;P, or Fitch, respectively. We have established guidelines relative to
    diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value Measurements</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and
    accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1,
    defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly
    traded biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale
    securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments
    from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value
    to the fair value based on observable market prices.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, Cash Equivalents and Investments</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term
    investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for
    identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our consolidated statements of
    operations. We use the specific identification method to determine the cost of securities sold.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have equity investments of less than 20 percent ownership in public and private biotechnology companies that we received as part
      of a technology license or partner agreement. At December 31, 2024, we held equity investments in <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_b448547c88c7434cbc329f97a4b3ea28" contextRef="c20241231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> publicly traded companies and <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_5091e6339b9e4e85943dd42b9d332383" contextRef="c20241231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">seven</ix:nonFraction> privately held companies.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our consolidated
    statements of operations. We account for our equity investments in publicly traded companies at their listed stock price. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting
    from observable price changes in orderly transactions for the identical or similar investment of the same issuer.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory in our consolidated balance sheets at the lower of cost or net realizable value under the first-in, first-out
    method, or FIFO. Our inventory costs include material, labor and overhead costs. Our raw materials include active pharmaceutical ingredient, or API, for commercial medicines. We capitalize inventory costs related to drug products when we consider
    future commercialization to be probable and expect to realize future economic benefit. When evaluating whether to capitalize inventory costs, we consider various factors, including the likelihood of receiving required regulatory approvals,
    communications from regulatory agencies such as safety or efficacy concerns, underlying manufacturing processes and supply chain matters, shelf life of the inventory, market trends such as competition and pricing, potential legal matters and potential
    reimbursement strategies. We record inventory costs that do not meet our capitalization requirements as R&amp;D expense in our consolidated statements of operations.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated
    net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory and historical write-offs.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We capitalize the costs of certain materials that we purchase for use in manufacturing our medicines in our clinical development programs
    because until we use these materials, they have alternative future uses. We can use these materials in multiple products and, as a result, each material has future economic value independent of the development status of any single medicine. We include
    capitalized materials in other current assets in our consolidated balance sheets and expense these costs as R&amp;D expenses when the materials are used. We review our capitalized materials periodically for continued alternative future use and reduce
    the carrying value of items in the period in which an impairment is identified.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2024, we reclassified capitalized costs related to materials used in our clinical development programs from inventories to other
    current assets in our consolidated balance sheets. As such, we reclassified the respective prior period amounts to conform with the current year presentation.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which we
    determine as the following (in years):</div>
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<div><br/>
  </div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 80.34%; vertical-align: bottom;"> </td>

    <td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Useful Lives</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software, laboratory, manufacturing and other equipment</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_b828ac0b40e9470bb076f1ca83c087f8" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember_RangeAxis_MinimumMember" format="ixt-sec:duryear">3</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_55512527b3f64093815e4719a3a9da7a" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember_RangeAxis_MaximumMember" format="ixt-sec:duryear">10</ix:nonNumeric></div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building, building improvements and building systems</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_d29ce71868244871b343b50d2485de0e" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember_RangeAxis_MinimumMember" format="ixt-sec:duryear">15</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_dc8025be6cc74cca855f74c2367e8b3f" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember_RangeAxis_MaximumMember" format="ixt-sec:duryear">40</ix:nonNumeric></div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land improvements</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_ebc4b025a1eb42b69cfea73de031e5b1" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_LandImprovementsMember" format="ixt-sec:duryear">20</ix:nonNumeric></div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leasehold improvements</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_a08cac9f5411485898c11087f1bef572" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember_RangeAxis_MinimumMember" format="ixt-sec:duryear">5</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_bda92ab03ee44df391ef93ce2060a192" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember_RangeAxis_MaximumMember" format="ixt-sec:duryear">15</ix:nonNumeric></div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_8596a99804394834b242d29ed1c6c554" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember_RangeAxis_MinimumMember" format="ixt-sec:duryear">5</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_2dd75df24eaa415ab54d1ac7e3d92e45" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember_RangeAxis_MaximumMember" format="ixt-sec:duryear">10</ix:nonNumeric></div>
        </td>

  </tr>


</table>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived
    assets, which include property, plant and equipment, for impairment whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>
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  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. We estimate our liability
    for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to third-party clinical management
    costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted
    fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these costs may differ
    materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>
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  </div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt</div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for each of our convertible debt instruments as a
      single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt
      issuance costs as contra-liabilities in our consolidated balance sheets at issuance and amortize them over the contractual term of the convertible debt instrument using the effective interest rate. </span>The<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> balances of our convertible senior notes presented in our consolidated balance sheets represent the principal balance of each convertible debt instrument less debt issuance costs.</span></div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024, we
    had <ix:nonFraction name="ions:DebtInstrumentNumberOfConvertibleNotes" id="Fact_10f5114021fc4f5bb04196fe30354c8a" contextRef="c20241231" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> outstanding convertible senior notes, our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_0da40ce130a0427ca4507455e50f00de" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>%
    Notes, which mature in June 2028, and our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_88cf15606ae648ba879a91ce9224095e" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes, which mature in April 2026. Our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_637081ace1c3467395b29f412ee7c215" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes matured in December 2024. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and
      Commitments</span>, for further details on our convertible senior notes.</div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-15</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Call Spread</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the issuance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fe2e410b891c4e8f90e9c7af0b2fd97c" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%
    Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ad09e792f7534196a47d6e0a5fba48da" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of
    purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not
    meet the definition of a liability using the guidance contained in ASC Topic 480; therefore, we account for the note hedges and warrants using the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Derivatives







      and Hedging &#8211; Contracts in Entity&#8217;s Own Equity</span> accounting guidance contained in ASC Topic 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified
    in shareholders&#8217; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our consolidated balance sheets. We reassess our ability to continue to classify any
    outstanding note hedges and warrants in shareholders&#8217; equity at each reporting period. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for
    further details on the call spread transactions. </div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Liability Related to Sale of Future Royalties</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. Under our agreement with Royalty Pharma, we record upfront payments and milestone payments we receive from the sale of future
    royalties as a liability, net of transaction costs. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for further details on the agreement.</div>
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  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We record royalty payments made to Royalty Pharma as a reduction of the liability or accrued interest and amortize the transaction costs
    over the estimated life of the royalty stream. We account for the associated interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the
    related product and recognizes the related revenue.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense using our
    current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material
    change in our estimate, we will prospectively adjust the effective interest rate and the related interest expense.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Leases</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use
    operating lease asset and associated short- and long-term operating lease liability in our consolidated balance sheets for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term
    and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we
    will pay over the lease term.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal
    options if we conclude we are reasonably certain to exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease
    term.</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information
    available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease.
    Our leases do not include material variable or contingent lease payments. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-16</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recent Accounting Standards</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2023, the Financial Accounting Standards Board, or FASB, issued Accounting Standard Update, or ASU, 2023-07, which provides
    updated guidance on segment reporting. The guidance requires public companies to disclose significant expenses that are regularly provided to the CODM, other segment items for each reportable segment and measures of segment profit or loss used by the
    CODM for allocating resources. In addition, the updated guidance requires public companies with a single reportable segment to provide all disclosures required under ASC 280, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Reporting</span>, and public companies to include in interim reports all disclosures related to a reportable segment&#8217;s profit or loss and assets that are currently required in annual reports. This update is effective for
    annual periods beginning after December 15, 2023 and interim periods beginning after December 15, 2024. The guidance is applied on a retrospective basis for all periods presented in the financial statements, unless it is impracticable. We adopted the
    annual reporting requirements in our 2024 Annual Report on Form 10-K. We expect to adopt the interim reporting requirements in our Quarterly Report on Form 10-Q in the first quarter of 2025. Refer to Note 12, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Information</span>, for further details on our segment information.</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2023, the FASB issued ASU 2023-09, which provides updated guidance on income tax disclosures. The new guidance requires
    companies to provide additional disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions and
    unrecognized deferred tax liabilities. This update is effective for annual periods beginning after December 15, 2024. Early adoption of this guidance is permitted. The guidance may be applied on a prospective or retrospective basis. We currently plan
    to adopt this guidance in our 2025 Annual Report on Form 10-K.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2024, the FASB issued ASU 2024-03, which requires public companies to disclose disaggregated expenses for certain expenses in
    the income statement. This update is effective for annual periods beginning after December 15, 2026 and interim periods within annual periods beginning after December 15, 2027. Early adoption of this guidance is permitted. The guidance may be applied
    on a prospective or retrospective basis. We are currently assessing the impact and timing of adopting this update.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2024, the FASB issued ASU 2024-04 to clarify the guidance for determining whether to account for early settlements of
    convertible debt as induced conversions or extinguishments. This update is effective for annual periods beginning after December 15, 2025 and interim periods within those annual periods. Early adoption of this guidance is permitted. The guidance may be
    applied on a prospective or retrospective basis. We are currently assessing the impact and timing of adopting this update.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any other recently issued accounting standards to have a material impact to our financial statements or disclosures.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2. Supplemental Financial Data</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventories</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryFinishedGoods" id="Fact_24167fa6e6d442398490541d6ad73f36" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">154</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventories</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_4803a14d03d74237b17f8d63e8173b4c" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,512</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_346da7c3659d43908f2c18156ff2131f" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,441</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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  </div>
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  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-17</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
<div><ix:continuation id="Text_d851c54a83904dd799150f30d08aa2259" continuedAt="Text_d851c54a83904dd799150f30d08aa22510">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>
</ix:continuation>

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  <ix:continuation id="Text_d851c54a83904dd799150f30d08aa22511" continuedAt="Text_d851c54a83904dd799150f30d08aa22512"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentTextBlock" id="Text_2add9cef486d4c08a940716c68c05cb1" contextRef="c20240101to20241231" escape="true" continuedAt="Text_9637ca96ef564e8995d903462c87de951">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our property, plant and equipment consisted of the following (in thousands):</div>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td style="background-color: #CCEEFF; vertical-align: bottom; white-space: nowrap; width: 76%;">
          <div style="text-align: left; margin-left: 6.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software, laboratory, manufacturing and other equipment</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_3f415076adb64aefb62a6200aa09373b" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">86,540</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_853375bcf45b4e2292895881e2f2165f" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">79,885</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building, building improvements and building systems</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_be347fecf99442269a1147ce15f0acde" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">41,228</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_55e9ea1cd6d04777a5fd335b1d632465" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">41,228</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leasehold improvements</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_8771d2aee3184880a9f8683acca837e9" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">54,375</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_afa97b7033ec449abdf9f88c730430b3" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,276</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_0a06832d59cb4e7b9ffef331f3c9e8f6" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,855</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_91cf4808a4ff4d89b617433a31ee3716" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,844</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_7f69b083e88341d0a10c7007be88479a" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">191,998</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_3f9477a2105042be8cc52f98c29cba1b" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">159,233</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Accumulated depreciation</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" id="Fact_f5a1f6ad7d4e4b6b8e9550921b213332" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">106,316</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" id="Fact_be9d2cd137b9488d8e04e6515601bea3" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">96,759</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentNet" id="Fact_4007d53a89214452be36c3718789c2f6" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">85,682</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentNet" id="Fact_8455ab90089d4679b0ea871acfd5ffa0" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">62,474</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; margin-left: 33.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;Total</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>
</ix:continuation>
  <ix:continuation id="Text_d851c54a83904dd799150f30d08aa22516" continuedAt="Text_d851c54a83904dd799150f30d08aa22517">
<div><br/>
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</ix:continuation>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our accrued liabilities consisted of the following (in thousands):</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
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</ix:continuation></ix:continuation>
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Clinical expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AccruedClinicalDevelopmentExpenses" id="Fact_a67b9aa3ded9444ea6fa8750f375469c" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">77,436</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AccruedClinicalDevelopmentExpenses" id="Fact_6080a8023b8a4a7680a671237d572043" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">105,967</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In-licensing expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AccruedCommercialExpensesCurrent" id="Fact_a85290633cb748aa801b0128951ad078" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,589</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AccruedCommercialExpensesCurrent" id="Fact_6e4c39c15d234eb09c433b9792328307" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,875</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other miscellaneous expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAccruedLiabilitiesCurrent" id="Fact_159ba94a17f648459aba5b5549ce591d" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">19,462</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total accrued liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_c527b3021abd4093a2c21fd084cef7d4" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">108,438</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_8efb348efdaa4293a28fe2308d0572ac" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">147,894</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation></div>

  <div style="text-align: left;"><br/>
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<div><ix:nonNumeric name="us-gaap:RevenueFromContractWithCustomerTextBlock" id="Text_8fa4a07991ac4286b221053dfdaeed02" contextRef="c20240101to20241231" escape="true" continuedAt="Text_448d78e7fce04d8d9b6f0aedad4003321">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3. Revenues</div>
</ix:nonNumeric>

  <ix:continuation id="Text_448d78e7fce04d8d9b6f0aedad4003321" continuedAt="Text_448d78e7fce04d8d9b6f0aedad4003322">
<div><br/>
  </div>
</ix:continuation>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">During the years ended December 31, </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2022, our revenues were comprised of the following (in
    thousands):</div>
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<div><br/>
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</ix:continuation></ix:continuation>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fa6507c61eec4896be131baaf9c56b33" contextRef="c20240101to20241231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">216,090</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_307e8969959e4a24a6efc7af51b04c5e" contextRef="c20230101to20231231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">240,379</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7fc25e4d7b6b4b3a9dcd1da1e35355ad" contextRef="c20220101to20221231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">242,314</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_91fef44f3ee5463aa3ae335c5e23e483" contextRef="c20240101to20241231_ProductOrServiceAxis_WainusRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,207</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6399ca8a95b34dcd85dbc52ace5b4853" contextRef="c20230101to20231231_ProductOrServiceAxis_WainusRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_39fbf4c0423d456cafb31165ea974914" contextRef="c20220101to20221231_ProductOrServiceAxis_WainusRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other commercial revenue:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA revenue, net</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6cd052c05ceb47d49deda22d54c0c1ce" contextRef="c20240101to20241231_ProductOrServiceAxis_ProductMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">34,189</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c355dfc232824d7a8157d578469c091c" contextRef="c20230101to20231231_ProductOrServiceAxis_ProductMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">34,913</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_8b3a41632c384aeda1287333d233f68b" contextRef="c20220101to20221231_ProductOrServiceAxis_ProductMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">30,051</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_401ed145ce1a4007b5d6f680d6d4fd33" contextRef="c20240101to20241231_ProductOrServiceAxis_OtherMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">22,590</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_82e0cd3700064c48aead8f65da55a2ea" contextRef="c20230101to20231231_ProductOrServiceAxis_OtherMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">33,299</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_aa4209cf55ce4cbeaa8fde9e6026bf29" contextRef="c20220101to20221231_ProductOrServiceAxis_OtherMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">30,993</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total other commercial revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6f70a82eb7a84473b35769bc3132c08b" contextRef="c20240101to20241231_ProductOrServiceAxis_OtherCommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">56,779</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_abce38c33594412d8019826b48d13405" contextRef="c20230101to20231231_ProductOrServiceAxis_OtherCommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">68,212</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_92aefda929294c40b3af86706f147a59" contextRef="c20220101to20221231_ProductOrServiceAxis_OtherCommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,044</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_03d2e1039bc445dd8b498d1d003c480c" contextRef="c20240101to20241231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">293,076</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d26daf2df3aa4029995f664eeaccb2e3" contextRef="c20230101to20231231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">308,591</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_8465172288b94b6fa2df19725f90d670" contextRef="c20220101to20221231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">303,358</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development revenue:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3db699190a8b445a8ca1d0999f8e2da6" contextRef="c20240101to20241231_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">332,647</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_37616169527f4d36aabceaa471579086" contextRef="c20230101to20231231_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">352,657</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA joint development revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d04c651ddd214f21b5d79968c12ce7df" contextRef="c20240101to20241231_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">79,415</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_92beb73be7ff41f484f6dd3f5c805c37" contextRef="c20230101to20231231_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">126,399</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_299c00c706f54824a2804eb5e1f44e71" contextRef="c20220101to20221231_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">76,787</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_89ebf294558547c785a5851eb6bc535d" contextRef="c20240101to20241231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">412,062</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3e5c4683f07442e4854d96729d89c815" contextRef="c20230101to20231231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">479,056</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f450bd3dc7c449ff8f7096209c42ed1d" contextRef="c20220101to20221231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">284,009</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: 54pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0fe1d38055094dcaa16865c239b63886" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">705,138</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e4607d0da0554ea281285854370d4b3c" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">787,647</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_52fe1890f7e84daf8e430adf09e21d37" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">587,367</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Revenue Sources</span></span>&#160;</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are sources of revenue and when we typically recognize revenue.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We earn commercial revenue primarily in the form of royalty
      payments on net sales of SPINRAZA and WAINUA. In </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we began earning royalties on net sales of WAINUA.</span></div>
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We earn commercial revenue from TEGSEDI and WAYLIVRA sales
      under our distribution agreements with </span>Sobi<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In addition, we receive royalties from</span> PTC Therapeutics International Limited, or PTC, for TEGSEDI and WAYLIVRA
    sales. Refer to Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, for details on our commercialization partnerships with Sobi and PTC.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also recognize as commercial revenue sales milestone payments and royalties we earn under our other collaborations.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In </span>December 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the FDA approved TRYNGOLZA (olezarsen) in the U.S. for the treatment of familial chylomicronemia syndrome, or FCS. Our launch of TRYNGOLZA is currently underway.</span></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaboration agreements</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration
    agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, R&amp;D services and manufacturing services.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the
    effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period,
    relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make
    numerous estimates and may use judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Upfront payments:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we enter into a collaboration agreement and receive an upfront payment, we record the entire upfront payment as deferred revenue if our only performance obligation is for
      R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. If part or all of the upfront payment is a license fee, we recognize as revenue the portion related to the license when
      we deliver the license to our partner because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Milestone payments:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We include variable consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they are
      achieved. We include these milestone payments when they are achieved because there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include regulatory milestone payments in the
      transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting
      rules.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, when we
    achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&amp;D services performance obligation and
    recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone payment to the
    transaction price.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the
    milestone event and we do not have a remaining performance obligation. For example, in 2024, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4d9d2b202ef043fab4e39a96a7369340" contextRef="c20240101to20241231_ProductOrServiceAxis_QalsodyMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">10</ix:nonFraction> million milestone payment from
    Biogen when the Ministry of Health, Labour and Welfare of Japan approved Biogen&#8217;s Japanese New Drug Application filing of QALSODY, which we recognized in full because we did not have any remaining performance obligations related to this milestone
    payment.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">License fees:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner because our partner has
      full use of the license and we do not have any additional performance obligations related to the license after delivery.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">WAINUA (Eplontersen) Collaboration with AstraZeneca</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize WAINUA for the
    treatment of transthyretin amyloidosis, or ATTR. Under the terms of the agreement, we received a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_6bb92631bcb24cecb14c1db01373726d" contextRef="c20210101to20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment in 2021. Refer to
    Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, for further details on this collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our WAINUA collaboration under ASC 808 and identified <ix:nonFraction name="ions:NumberOfMaterialComponents" id="Fact_77244fc7a2e94cb79c8cbd4b24da3caa" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the
    co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_ba2c8e8b9b084f918923e87c66222bf9" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation. For our sole performance obligation, we determined the transaction price was the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_7a3ad0b9fdcd4f748e4e867ab2270c0c" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations
    after we delivered the license to AstraZeneca.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is currently responsible for <ix:nonFraction name="ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" id="Fact_5e87322def9b4973aefbf130af9125cb" contextRef="c20240101to20241231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">55</ix:nonFraction> percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an
    accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#8217;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing WAINUA to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related
    to commercial and medical affairs activities as reductions of our SG&amp;A expense and R&amp;D expense, respectively.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Swedish Orphan Biovitrum AB (Sobi)</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, we concluded that our performance obligation is to provide
    services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global
    commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished
    goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">WAINUA (Eplontersen) Collaboration</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for
    the treatment of ATTR. The FDA and Health Canada approved eplontersen with the brand name, WAINUA, for hereditary ATTR, or ATTRv-PN, while the Medicines and Healthcare products Regulatory Agency, or MHRA, approved WAINUA for ATTRv-PN in the United
    Kingdom, or UK, as WAINZUA. Under the agreement, we are jointly developing WAINUA with AstraZeneca worldwide for ATTRv-PN and ATTR cardiomyopathy, or ATTR-CM. We are jointly commercializing WAINUA with AstraZeneca in the U.S. We granted AstraZeneca
    exclusive rights to commercialize WAINUA outside the U.S.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Over the term of the collaboration, we are eligible to
      receive up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_79969c9a9b914450bc63737b97f2fd7e" contextRef="c20241231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">3.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion, which is comprised of a $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_9dd7d53c8eee485eacad6e97dffdd4c2" contextRef="c20210101to20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment, up to $</span><ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_7c6f989ad85b49c8b6bfede72712bef2" contextRef="c20241231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">485</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development and approval milestone payments and up to $</span><ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_062b2352c9f546cca5d16c63150ff4fa" contextRef="c20241231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">2.9</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in sales milestone payments. The agreement includes
      territory-specific development, commercial and medical affairs cost-sharing provisions. In addition, we are eligible to receive up to mid-</span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" id="Fact_0b4829fbe9d847069807a9be4cf64ebe" contextRef="c20240101to20241231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.S. From inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_7469eb0249ca4ffcac8492eb70284535" contextRef="c20241231_RangeAxis_MinimumMember_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">465</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration. We will achieve the next payment of $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_4a0bd116585244199074e8ebf6cce950" contextRef="c20241231_RangeAxis_MaximumMember_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million or $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_688b9b03995046109c5d3da29da27b5b" contextRef="c20241231_RangeAxis_MinimumMember_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">115</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upon regulatory approval of WAINUA for ATTR-CM in the U.S. or Europe, respectively, under
      this collaboration.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. As a result, we began earning
    royalties from WAINUA sales, which we recognize as commercial revenue in our consolidated statements of operations.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our WAINUA collaboration under ASC 808 and identified <ix:nonFraction name="ions:NumberOfMaterialComponents" id="Fact_d4f80df42eb24e19af6957ccd65c9827" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca will perform, (iii) the co-commercialization
    activities that we and AstraZeneca will perform and (iv) the co-medical affairs activities that we and AstraZeneca will perform.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_4fa62bc3f1be4c069e70a0000c4e2a73" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation. For our sole performance obligation, we determined the transaction price was the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_44e63366a6fb46c893bca11b7dcc2c44" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment we received in 2021. In 2023, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_79e35c2309284a009d4d2169f9d0c3eb" contextRef="c20230101to20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction> million license fee payment when we licensed rights to Latin America for WAINUA to AstraZeneca. We recognized these payments in full because we did not have any remaining performance obligations after we delivered the
    licenses to AstraZeneca.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration. AstraZeneca is currently responsible for <ix:nonFraction name="ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" id="Fact_d54fda2f005e411087fa50cc25d7061d" contextRef="c20240101to20241231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">55</ix:nonFraction> percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we recognize as revenue the <ix:nonFraction name="ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" id="Fact_cdef7d861b704faaa5f351d6c9d584db" contextRef="c20240101to20241231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">55</ix:nonFraction> percent of cost-share funding AstraZeneca is responsible for in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing WAINUA to market outside the U.S., we recognize cost-share funding we receive from AstraZeneca related to these activities as a reduction of
    our commercial and medical affairs expenses. In the fourth quarter of 2024, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5f460923a7ec4d5d89e967c94b57f904" contextRef="c20241001to20241231_ProductOrServiceAxis_AttrvPnMember_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">30</ix:nonFraction> million milestone payment from AstraZeneca when the
    MHRA approved WAINZUA for ATTRv-PN in the UK. We recognized this milestone payment in full as joint development revenue because we did not have any remaining performance obligations related to the milestone payment.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Cardiovascular, Renal and Metabolic Collaboration</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our collaboration for WAINUA, we have a collaboration with AstraZeneca focused on discovering and developing treatments for
    cardiovascular, renal and metabolic diseases, which we formed in 2015. In December 2024, we amended this collaboration agreement with AstraZeneca. The amendment changed future potential milestone payments and royalties we could receive under the
    collaboration. We determined there were no changes that would require adjustments to revenue we previously recognized because we had no ongoing performance obligations under the agreement. Under our collaboration, AstraZeneca has licensed multiple
    medicines from us. AstraZeneca is responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed from us.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_8a9caf1ea009432aa464f4d2fbf3e279" contextRef="c20241231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">4.3</ix:nonFraction> billion, which is comprised of a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_afe0e303f52c47de8fef2665adbb52f3" contextRef="c20150101to20151231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction> million upfront payment, up to $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_7cd4f898b49c4221a2cec4bcbec84b73" contextRef="c20241231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">175</ix:nonFraction> million in license fees, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_c41eea94f6c04393af0bccfd93fed8b5" contextRef="c20241231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">514</ix:nonFraction> million
    in development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_838fed161cbc4c51b3a1d3b9427e01a6" contextRef="c20241231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">863</ix:nonFraction> million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_844d1a7f57c745c5b8fd335b3209017f" contextRef="c20241231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">2.8</ix:nonFraction> billion in sales milestone payments. In addition, we are eligible to receive tiered royalties up to <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_ead385b2ed3c447f99d4747df275c027" contextRef="c20240101to20241231_RangeAxis_MaximumMember_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">10</ix:nonFraction> percent on net sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. From inception through December 31, 2024, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_b46d3be360f94ea788b2b83ce6c73f6f" contextRef="c20241231_RangeAxis_MinimumMember_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">340</ix:nonFraction>
    million in payments under this collaboration. We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_2b949e7c63b941a3955f5c01227834d5" contextRef="c20241231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">30</ix:nonFraction> million if AstraZeneca advances a medicine under this
    collaboration<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_12852f4c3cee4a69b4f4fee5d29498e6" contextRef="c20150731_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for AstraZeneca. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_321f6d91fea64a57a4103c135ba57bd1" contextRef="c20150731_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction>
    million upfront payment we received and we allocated it to our single performance obligation. We recognized revenue for our R&amp;D services performance obligation as we performed services based on our effort to satisfy this performance obligation
    relative to our total effort expected to satisfy our performance obligation. We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> completed our performance obligation in</span> 2021. As we achieved milestone payments for our
    R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. From inception through the completion of our performance obligation, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_ec77e25e50654249ba1ef8f5f9e4a1d1" contextRef="c20241231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">90</ix:nonFraction> million in payments in the transaction price for our R&amp;D services performance obligation.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance
    obligation. We recognized each of these payments in full in the respective period we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. For example, in the fourth quarter
    of 2024, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4d1e5d003192488c85affd353eff20db" contextRef="c20241001to20241231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction> million payment when AstraZeneca licensed a compound from us. We recognized this payment in full in 2024 because we did
    not have any remaining performance obligations after we delivered the license to AstraZeneca.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts):</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

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    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with AstraZeneca</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_77009387bc654006989ae141c96c8496" contextRef="c20240101to20241231_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">129,759</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b4bc1487977543468f0c2592f732bfb0" contextRef="c20230101to20231231_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">202,236</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6f993bce8b8f4c7aa2348aedba4438cf" contextRef="c20220101to20221231_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">79,160</ix:nonFraction></div>
        </td>

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          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_146be9f3b2bd4a1390bcfa5173d38d88" contextRef="c20240101to20241231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">18</ix:nonFraction></div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_dd338796e71247f6bc131ed50f37ef36" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">26</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_aa247af696394bd6806e0b89dffcff91" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">13</ix:nonFraction></div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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  </tr>


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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_b22d4dca96604e1cb60121e3c991236b" contextRef="c20241231_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_cfd27ca80d9f460e8f3e825d0b1607b2" contextRef="c20231231_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t have any
    deferred revenue from our relationship with AstraZeneca at December 31, 2024 and 2023.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Biogen</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Marketed Medicines</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2012, we entered into a collaboration agreement with
      Biogen to develop and commercialize SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we received more than $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_a14b040f8a544476a4a93f96bfb2d9ea" contextRef="c20241231_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">2.2</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in total payments under this collaboration, including approximately
      $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_6b4f0a623d7d4e51a4b87d093638d5ca" contextRef="c20241231_ProductOrServiceAxis_SpinrazaRoyaltiesMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.8</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion from SPINRAZA royalties and more than $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_7a1ae789462443c5918ce08f602a82e6" contextRef="c20241231_ProductOrServiceAxis_SpinrazaResearchAndDevelopmentMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">425</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from R&amp;D revenue. We are receiving tiered royalties ranging
      from </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_178dd43e6f904dd28de7f2e04d95e8a1" contextRef="c20240101to20241231_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">11</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_a289d94508ca478980b0f42285953e4d" contextRef="c20240101to20241231_RangeAxis_MaximumMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">15</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales of SPINRAZA. We have exclusive in-licensed patents
      related to SPINRAZA from Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on net sales of SPINRAZA. Biogen is responsible for all
      global development, regulatory and commercialization activities and costs for SPINRAZA. We completed our performance obligations under this collaboration in 2016</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2023, we entered into a royalty purchase agreement with Royalty Pharma in which Royalty Pharma receives <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_7ac830af0c6f44a4b2aa6ce6796ffb9d" contextRef="c20241231_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_2f734443dd48448fae9f196b007caa2d" contextRef="c20241231_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">45</ix:nonFraction> percent of royalty payments in 2028, on up to $<ix:nonFraction name="ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" id="Fact_e4de0394b76640d3a5ee40e963853271" contextRef="c20241231_ProductOrServiceAxis_SpinrazaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.5</ix:nonFraction> billion in annual
    sales. Royalty Pharma&#8217;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $<ix:nonFraction name="ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" id="Fact_4a64a983386747d1955c46c5a1f3c0af" contextRef="c20241231_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">475</ix:nonFraction>
    million or $<ix:nonFraction name="ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" id="Fact_ac923f23102e41ee8be21dedeb32c303" contextRef="c20241231_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">550</ix:nonFraction> million, depending on the timing and occurrence of the U.S. Food and Drug Administration, or FDA, approval of pelacarsen, which
    Novartis is developing. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for further discussion of this agreement.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">QALSODY</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2018, Biogen exercised its option to license QALSODY, our medicine that received accelerated approval from the FDA in April 2023 and
    marketing authorization under exceptional circumstances from the European Medicines Agency, or EMA, in May 2024 for the treatment of adult patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS. As a result, Biogen is
    responsible for global development, regulatory and commercialization activities and costs for QALSODY. Biogen is also evaluating QALSODY as a potential treatment for presymptomatic SOD1-ALS patients in the ongoing ATLAS study. From inception through December 31, 2024, we received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_3ec00ba116c2419fab23934bb1d041ec" contextRef="c20241231_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaboration2013NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">110</ix:nonFraction>
    million in total payments under this collaboration, including approximately $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_cd475d66ed7644c892f5202758de970e" contextRef="c20241231_ProductOrServiceAxis_QalsodyRoyaltiesMember_TypeOfArrangementAxis_BiogenCollaboration2013NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">3</ix:nonFraction> million from QALSODY royalties and $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_50d2e149bb3c41828645f28ad029a349" contextRef="c20241231_ProductOrServiceAxis_QalsodyResearchAndDevelopmentMember_TypeOfArrangementAxis_BiogenCollaboration2013NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">108</ix:nonFraction> million from R&amp;D revenue. We are receiving tiered royalties ranging from <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_5575ecc5ea9940d2826dc1a9e2246880" contextRef="c20240101to20241231_ProductOrServiceAxis_QalsodyMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaboration2013NeurologyMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">11</ix:nonFraction> percent to <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_c6ec0ca82809470c8bd915b587d00c03" contextRef="c20240101to20241231_ProductOrServiceAxis_QalsodyMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_BiogenCollaboration2013NeurologyMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">15</ix:nonFraction> percent on net sales of QALSODY. We completed our
    performance obligations under this collaboration in 2020.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">New Antisense Medicines for the Treatment of SMA</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2017, we entered into a collaboration agreement with
      Biogen to </span>identify <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense medicines for the treatment of SMA</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At the commencement of this collaboration, we received a </span>$<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_29c1e40d3f0c4c55bf09a3c02670fd97" contextRef="c20170101to20171231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction> million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> upfront payment from Biogen. In </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2021</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Biogen exercised its option to license ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">306</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, a drug we discovered under this collaboration, for which </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">we earned a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_181e9f5014a047a0927932cac3b4a590" contextRef="c20210101to20211231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee payment. We recognized this payment as revenue in full because</span> Biogen had full use of the license without any continuing involvement from us. Biogen is solely responsible for the costs and
    expenses related to the development, manufacturing and potential future commercialization of ION306 following the option exercise. We do not have any remaining performance obligations under this collaboration. <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We will receive development and regulatory milestone payments from Biogen if new medicines, including ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">306</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, advance towards marketing approval.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_dd53fcd3fa6e43f09211c80f06ab28db" contextRef="c20241231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">555</ix:nonFraction> million if Biogen advances ION306, which is comprised of up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_76eea149c620492e8f99b512e1a3d282" contextRef="c20241231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">45</ix:nonFraction>
    million in development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_24f565e1839448abb8bdfad937290640" contextRef="c20241231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">110</ix:nonFraction> million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_688dc7505cbd409ebc47edc47dbe1c66" contextRef="c20241231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">400</ix:nonFraction> million in sales milestone payments. In addition, we are eligible to receive tiered royalties <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">from the mid-teens to </span>mid-<ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_161010e4ed3540c6bde7b9d15473ca2a" contextRef="c20240101to20241231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent range <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">on net sales from any product that Biogen successfully commercializes under this collaboration.</span> From inception through December 31, 2024, we received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_7f76f6cbb5bf458e88ad0dc79797d110" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">85</ix:nonFraction> million in payments under this
    collaboration. We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_91e1c28fec9849f1ba3e40725bf62eb0" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">45</ix:nonFraction> million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">if Biogen initiates a Phase 3 trial under this collaboration.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Neurology Collaborations</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have multiple collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders,
    including our 2018 and 2012 neurology collaborations. Under these collaborations, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for certain neurological diseases and the option to license certain medicines
    resulting from these collaborations. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine.</div>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-22</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our 2018 neurology collaboration, we are currently advancing multiple programs. For each medicine under this collaboration, we are
    eligible to receive <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" id="Fact_c889cffdc9884f8bb477e534a72fa537" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2018NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">270</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is comprised of a $</span><ix:nonFraction name="ions:MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" id="Fact_69c105fa3eee42319102e726aada6eab" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2018NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee, up to $</span><ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" id="Fact_c404586cb38c42d385182d2db0d52056" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2018NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">105</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestone payments and up to $</span><ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" id="Fact_475e56d73bee434790e94a47aa02a543" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2018NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">150</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone payments</span>. In addition, we are eligible to receive tiered royalties up to
    the <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_8357116b96394e8fb13320efb45baded" contextRef="c20240101to20241231_TypeOfArrangementAxis_BiogenCollaboration2018NeurologyMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent range on net sales from any product that Biogen successfully commercializes under this collaboration. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received nearly $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_9e57fed80a9f42b29a40ce59e5d5b629" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2018NeurologyMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.1</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in payments under this collaboration, including payments to purchase our stock. </span>We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_c998cf26eab54d4c8cbef789c3839ac0" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2018NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction> million if Biogen licenses a medicine under this collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of our 2018 neurology collaboration, we determined our transaction price to be $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_649b6114f7b148adb8293fc7cb513c34" contextRef="c20180430_TypeOfArrangementAxis_BiogenCollaboration2018NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">552</ix:nonFraction> million, comprised of $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_295441e12b2641d7bb800b42a8eb179a" contextRef="c20180401to20180630_TypeOfArrangementAxis_BiogenCollaboration2018NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">375</ix:nonFraction> million from the upfront payment and $<ix:nonFraction name="ions:PremiumPaidOnSharesPurchased" id="Fact_91807674ec324f3b9de9844e55331c0e" contextRef="c20180401to20180630_TypeOfArrangementAxis_BiogenCollaboration2018NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">177</ix:nonFraction> million for the premium paid by Biogen for its purchase of our common stock. We allocated the transaction price to our single performance obligation,
    which was to perform R&amp;D services for Biogen. From inception through December 31, 2024, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_b639bb42a0c94166b56427b85b1cb985" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2018NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">623</ix:nonFraction> million in upfront and milestone payments in the transaction price for our R&amp;D services performance obligation. We recognize revenue for our R&amp;D
    services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance
    obligation at the end of the contractual term in June 2028.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our 2012 neurology collaboration, Biogen exercised its option to license IONIS-MAPT<sub>Rx</sub>, an investigational RNA-targeted
    medicine for the potential treatment of Alzheimer&#8217;s disease, or AD, in 2019. As a result, Biogen is responsible for global development, regulatory and commercialization activities and costs for IONIS-MAPT<sub>Rx</sub>. We are eligible to receive up to
    $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_2667cb05a38a481e8877646026e5272a" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">185</ix:nonFraction> million for the IONIS-MAPT<sub>Rx</sub> program, which is comprised of a license fee of $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_60badd26caf1411893cc6137b0779dda" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">45</ix:nonFraction> million, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_93bde0adf28c44c78e25e187945ee0af" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">10</ix:nonFraction> million in development milestone payments and up to
    $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_7e6e451a8ed24ecc9e8715b640d26f87" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">130</ix:nonFraction> million in regulatory milestone payments, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. In addition, we are eligible to
    receive tiered royalties up to the mid-teens on net sales of any medicines resulting from the IONIS-MAPT<sub>Rx</sub> program. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_fb63522f1ba244df9cf77b67f9b78db3" contextRef="c20241231_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">230</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration. </span>We will achieve the
    next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_9064c28b3af344b7a759e821fed7a1ef" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction> million if Biogen advances MAPT<sub>Rx</sub> into Phase 3 development under this collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of our 2012 neurology collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_ecd97743d24d44e8b045f5d1b091ef34" contextRef="c20121231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> separate performance obligations as our development work for IONIS-MAPT<sub>Rx</sub> and ION582. We completed our R&amp;D services performance obligations for IONIS-MAPT<sub>Rx</sub>
    and ION582 in 2022 and 2024, respectively. From inception through the completion of our performance obligations, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_c834c565c10243e5b3ff08ce30af205c" contextRef="c20241231_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">57</ix:nonFraction> million in
    the transaction price for our IONIS-MAPT<sub>Rx</sub> development performance obligation. From inception through the completion of our performance obligations, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_44aab42fb8674539922ef1112fa787f4" contextRef="c20241231_ProductOrServiceAxis_Ion582Member_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">68</ix:nonFraction> million in milestone payments in the transaction price for our ION582 development performance obligation. We recognized revenue for our R&amp;D services performance obligations
    as we performed services based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the second quarter of 2024, Biogen&#8217;s option to license ION582, an investigational antisense medicine for the potential treatment of
    Angelman syndrome, or AS, expired unexercised. As a result, we recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ba6a7db142ba437fa21be2b45c050da3" contextRef="c20240401to20240630_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">30</ix:nonFraction> million of R&amp;D revenue from previously deferred milestone
    payments related to the ION582 study because we did not have any remaining performance obligations.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts):</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Biogen</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_403d9cda527942eebe653e237a09e0d2" contextRef="c20240101to20241231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">368,058</ix:nonFraction></div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2ebfafb3c5bc4279ac6f1fe0d881ca3c" contextRef="c20230101to20231231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">350,146</ix:nonFraction></div>
        </td>

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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_80a7b14f723f4263ac28bb9cea37c9f3" contextRef="c20220101to20221231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">366,696</ix:nonFraction></div>
        </td>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_62a0af8fdbf545ceaf2e20b54e1b39e9" contextRef="c20240101to20241231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">52</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_d850727932c64a3997760ce5c8a27e6e" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">44</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_03d677a830694c75a9a7cc4221bd89b5" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">62</ix:nonFraction></div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_675dc57316e24e2eba16c5c38da7a0d0" contextRef="c20241231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">211.0</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_deb3b72ca92141249addc59d7901ef3b" contextRef="c20231231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">307.4</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, from our relationship with Biogen.</span></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">GSK</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2010, we entered into a collaboration with GSK using our antisense drug discovery platform to discover and develop new medicines
    against targets for serious and rare diseases, including infectious diseases. Upon initiating the collaboration, we received an upfront payment of $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_df9eb741d1a047928581ba9b172e1706" contextRef="c20100101to20101231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction>
    million. Under our collaboration, GSK is developing bepirovirsen for the treatment of chronic hepatitis B virus infection, or HBV, infection. In 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global
    development, regulatory and commercialization activities and costs for the HBV program.</div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-23</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive nearly $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_4efd385d112840afad0e4faa46214870" contextRef="c20241231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">260</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_015e4506f3a84a70b7751dae7cadee18" contextRef="c20241231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction> million license fee, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_229776738d884ce8aee54ac341784a2d" contextRef="c20241231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">42.5</ix:nonFraction> million in development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_131e23080dcc40398152b2bd4d048056" contextRef="c20241231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">120</ix:nonFraction>
    million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_a5c67dd2e09b4b708ea1ffa029688a59" contextRef="c20241231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">70</ix:nonFraction> million in sales milestone payments if GSK successfully develops and commercializes
    bepirovirsen. In addition, we are eligible to receive tiered royalties up to the low-teens on net sales of bepirovirsen. From inception through December 31, 2024, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_80b40aad4e4f428d854cce06e968dea2" contextRef="c20241231_RangeAxis_MinimumMember_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">105</ix:nonFraction> million in an upfront payment and payments related to the HBV program.</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We completed our R&amp;D services performance obligations in 2015. Therefore, we do not have any remaining performance obligations under
    our collaboration with GSK. However, we can still earn additional payments and royalties as GSK advances the HBV program.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> In 2023, we earned a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7a180d97974b46aaa98d1cc7173130c8" contextRef="c20230101to20231231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment when GSK initiated a Phase 3 program of
      bepirovirsen. We recognized this milestone payment as R&amp;D revenue in full in 2023 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next payment of $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_7ef9cac4d3634dc28f74729428a263ab" contextRef="c20241231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if the FDA accepts an NDA filing of bepirovirsen for review.</span></div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with GSK (in thousands, except percentage amounts):</div>
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<div><br/>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with GSK</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_1efa0cc60e004562b4e6a6c7879c789d" contextRef="c20240101to20241231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c2187b192cd648f1950547dfeb6f407a" contextRef="c20230101to20231231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,000</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ec6cf4febb2f49e683915746e6801969" contextRef="c20220101to20221231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_fcadd36b6cbc4c4796ae789c7805b00f" contextRef="c20240101to20241231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_ff3be5276ecf4d51a2514c2feff18233" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">2</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_64cbaaeaf4c249c28f7644f151cd8a75" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_b211069271df4c4a802417ef5e7b0d32" contextRef="c20231231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_59e8ee0b0973416987e4c07862acaea5" contextRef="c20241231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t have any
    deferred revenue from our relationship with GSK at December 31, 2024 and 2023.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Novartis</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Pelacarsen Collaboration</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2017, we initiated a collaboration with Novartis to
      develop and commercialize pelacarsen.</span> Novartis is responsible for conducting and funding development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study that Novartis initiated in 2019.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_34bc42390fa34a3d9908bf5db5ae8531" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">900</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_5c0bfffb36654aff8e12544c8c26161d" contextRef="c20170101to20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">75</ix:nonFraction> million upfront payment, a $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_57d9ab1fc2ed47699a00a295669bf20a" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">150</ix:nonFraction> million license fee, a $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_b0160b60708f4f9cac5ee7648f0ee321" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction> million
    development milestone payment, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_788a557118454c209aecf3914c029c91" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">290</ix:nonFraction> million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_b32f437673cc4aac8bfcce020d51b7b0" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">360</ix:nonFraction> million in sales milestone payments. We are also eligible to receive tiered royalties in the mid-teens to low <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_016f76af44eb49289c02150198f2a523" contextRef="c20240101to20241231_ProductOrServiceAxis_PelacarsenActivePharmaceuticalIngredientMember_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent range on net sales of pelacarsen. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_f70b581c4c184bd7afb533f20dd7fa6d" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">275</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration. We</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> will achieve the next payment of $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_3b19b0a102744ca58f85eea2983e6a84" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">50</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if the FDA accepts an NDA filing for pelacarsen.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At the commencement of this collaboration, </span>we
    determined our transaction price to be $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_6dbe3e18253b42678289e91bfc07aa2b" contextRef="c20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">108.4</ix:nonFraction> million, comprised of the $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_5578c7a91e964f86994ba7891b038b6c" contextRef="c20170101to20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">75</ix:nonFraction> million from the upfront payment, $<ix:nonFraction name="ions:PremiumReceivedOnSharesIssued" id="Fact_a374896a5baf4a14a92524dbf907cb65" contextRef="c20170101to20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">28.4</ix:nonFraction> million for the premium paid
    by Novartis for its purchase of our common stock and $<ix:nonFraction name="ions:PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" id="Fact_844ad8b58c81489eb92908f6d9b9a1e0" contextRef="c20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.0</ix:nonFraction> million for the potential premium Novartis would have paid if they purchased our common
    stock in the future. We <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">identified </span><ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_45dfae68b384426d9e7f35800c5ee5da" contextRef="c20170331_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> separate performance obligations as the R&amp;D services and API for pelacarsen and olezarsen. We recognized revenue for our R&amp;D services performance obligations as we
      performed services </span>based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>We
    completed our R&amp;D services performance obligations for olezarsen and pelacarsen<sub>&#160;</sub>in 2019. As such, we recognized all revenue we allocated to the olezarsen and pelacarsen<sub>&#160;</sub>R&amp;D services as of the end of 2019. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through the completion of our performance obligations, we have included $</span><ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_39ed4f81430049f48c2b12bb9d3bd028" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">104</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments in the transaction price for our R&amp;D services performance obligations under this collaboration.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As described in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Biogen SPINRAZA</span>
    section above, in 2023, we entered into a royalty purchase agreement with Royalty Pharma. Under the agreement, in addition to a minority interest in SPINRAZA royalties, Royalty Pharma will receive <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_3449901b0f55449e94e939f4a2f1c065" contextRef="c20241231_ProductOrServiceAxis_PelacarsenActivePharmaceuticalIngredientMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of any future royalty payments on pelacarsen. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term
      Obligations and Commitments</span>, for further discussion of this agreement.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">New Medicine for the Treatment of Lp(a)-Driven Cardiovascular Disease</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2023, we entered into a collaboration and license agreement with Novartis for the discovery, development and commercialization
    of a novel medicine for patients with Lp(a)-driven cardiovascular disease, or lipoprotein(a)-driven CVD. Novartis is solely responsible for the development, manufacturing and potential commercialization of the next generation Lp(a) therapy.</div>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-24</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_e7f12a6400a4493abc4b2e919f3dec81" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">730</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_c526c9b3aac3498eba1daf4a7d4ed9b9" contextRef="c20231001to20231231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million upfront payment, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_35d21584d311403db335fec885d08698" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">155</ix:nonFraction> million in development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_820c0c4db93943189c8c0d43dce4586e" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">105</ix:nonFraction>
    million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_36bd04df93434800be4f1854ac45250e" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">410</ix:nonFraction> million in sales milestone payments. In addition, we are eligible to receive tiered
    royalties ranging from <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_5b492ad60db14f8a8bf151441f4aa1bf" contextRef="c20240101to20241231_RangeAxis_MinimumMember_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">10</ix:nonFraction> percent to <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_2c6c32bec6f34431ae2264d3cde44dc1" contextRef="c20240101to20241231_RangeAxis_MaximumMember_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent
    on net sales. From inception through December 31, 2024, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_992231ab48fe4d57af8fc641802cc712" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction> million from payments under this collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_b211469b14f24bd6859fae30e7995afc" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">10</ix:nonFraction>
    million if Novartis advances a medicine under this collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At the commencement of this collaboration, we identified </span><ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_5b04e66a2f85491eb8b7b3a42796fa13" contextRef="c20230831_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligation, which was to perform R&amp;D services for Novartis.
    </span>We recognized revenue for our R&amp;D services performance obligation as we performed services based on our effort to satisfy this performance obligation relative to our total effort expected to satisfy our performance obligation. We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> completed our performance obligation in</span> the third quarter of 2024. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction
    price for our R&amp;D services performance obligation.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> From inception through the completion of our performance obligation, we have included $</span><ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_81ba7d8fe40040e5b7ac1b6989c5d2c0" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in upfront and milestone payments in the transaction price for our
      R&amp;D services performance obligation under this collaboration.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Novartis (in thousands, except percentage amounts):</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Novartis</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_34a7cbc53ddb475aaaa8bcec238b44ce" contextRef="c20240101to20241231_TypeOfArrangementAxis_NovartisCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">37,762</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_cd2c4f63152b45998731917ab0309ed1" contextRef="c20230101to20231231_TypeOfArrangementAxis_NovartisCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">30,194</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4ff5f9c394c349349b7bc24fd95d7574" contextRef="c20220101to20221231_TypeOfArrangementAxis_NovartisCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">237</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_1f40d9d87ee4435c83ab9656d281b655" contextRef="c20240101to20241231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_NovartisCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">5</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_130e18fe0f0c441186a0e17a58f664d9" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_NovartisCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">4</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less than <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_3cbf0264fff04ba19d7c857cee72d9f4" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_NovartisCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>%</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>


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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our consolidated balance sheets at December 31, 2024 and 2023 included deferred revenue of $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_87d3106b1a1148dea7b789814a61c3f6" contextRef="c20241231_TypeOfArrangementAxis_NovartisCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_9cc8b6d4f47d49dda3cd784f5d573ef3" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">30.0</ix:nonFraction> million, respectively, from our relationship with Novartis.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Roche</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Sefaxersen
      (IONIS-FB-L</span><sub>Rx</sub><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">) for Complement-Mediated Diseases</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2018, we entered into a collaboration agreement with Roche to<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop sefaxersen (IONIS-FB-L</span><sub>Rx</sub>) for the treatment of complement-mediated diseases, including immunoglobulin A nephropathy, or IgAN, and geographic atrophy, or GA. In April 2023, Roche initiated a
    Phase 3 study of sefaxersen in patients with IgAN.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">After positive data from a Phase 2 clinical study in patients
      with IgAN, </span>Roche<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> licensed </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">sefaxersen</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2022</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_744c3b17aa014073b17689e15adf5a2a" contextRef="c20220101to20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. As a result, Roche is responsible for global development, regulatory and commercialization activities, and costs for sefaxersen. In 2022, we amended our sefaxersen
      collaboration agreement with Roche. The amendment changed future potential milestone payments we could receive under the collaboration. We determined there were no changes that would require adjustments to revenue we previously recognized.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In </span>July 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Roche discontinued development of </span>sefaxersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of GA, following the completion of the Phase </span>2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> study, which showed a favorable safety profile and target engagement, but insufficient efficacy to advance into Phase </span>3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> development.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Over the term of the </span>sefaxersen <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">collaboration for the treatment of IgAN, we are eligible to receive up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_5a1f4714bc0940e98047f54dde3feaf4" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">430</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is comprised of a $</span><ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_3fe5e1d10c814bc3a6a007cda65196f9" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee, up to $</span><ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_549abbde82e1406b93bf628bebb95927" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestone payments, up to $</span><ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_541e131f3c6b4c92914c6be252062f60" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">90</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone payments and up to $</span><ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_a41faf144bd64eda8d77e690e142dd36" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">280</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in sales milestone payments. In addition, we are also eligible to receive tiered royalties from the high teens to </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_8b43151140c6441594f417ab61eb2559" contextRef="c20240101to20241231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales.</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>From inception
    through December 31, 2024, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_c786e47ad0b540fbb376640b5b6b6aba" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">140</ix:nonFraction> million in payments under this collaboration. <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We will achieve the next payment of $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_5128247561064475b51c4c5bf62130be" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.5</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if Roche advances sefaxersen for the
      treatment of IgAN under this collaboration.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_468a8db7e8de46a69b5ee7a0575f664d" contextRef="c20181031_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Roche. We recognized revenue for our R&amp;D services performance obligation as we performed services based on our effort to satisfy this performance
    obligation relative to our total effort expected to satisfy our performance obligation. We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> completed our performance obligation in</span> the fourth quarter of 2024. As we
    achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. From inception through the completion of our performance obligation, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_f2a4482e638e473f8466afadc352df31" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">97</ix:nonFraction> million in upfront and milestone payments in the transaction price for our R&amp;D services performance obligation under this collaboration.</div>
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Huntington&#8217;s Disease</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2013, we entered into an agreement with Hoffmann-La Roche Inc and F. Hoffmann-La Roche Ltd, collectively Roche, to develop treatments
      for Huntington&#8217;s disease, or HD, based on our antisense technology. Under the agreement, we discovered and developed tominersen, an investigational medicine targeting HTT protein. We developed tominersen through completion of our Phase 1/2 clinical
      study in people with early-stage HD. In 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. As a result, Roche is responsible for all global development, regulatory and commercialization activities and
      costs for tominersen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_d8d42ebb32dc46b7895c83156cf73607" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">395</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" id="Fact_2675eccdc9c6499798e84c5ac5edaddf" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">30</ix:nonFraction> million upfront payment, a $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_28560f4cf8f840bf86e78770db9fa40e" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">45</ix:nonFraction> million license fee, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_70a5f7bc239446719e9285ed2ff78c07" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">70</ix:nonFraction> million in
    development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_884490256579410c93629768255d304a" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">170</ix:nonFraction> million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_a9fce437f8684220b259d8408d43875f" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">80</ix:nonFraction> million in sales milestone payments as tominersen advances. In addition, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" id="Fact_67793d8d7c8843aba2b236e8d909758e" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">136.5</ix:nonFraction> million in milestone payments for each additional medicine successfully developed. We are also eligible to receive tiered royalties up to the mid-teens on net sales of any
    product resulting from this collaboration. From inception through December 31, 2024, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_3aa74885781e415aa4fe5dd8e04e1eda" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">150</ix:nonFraction> million in payments under this collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_cb403b59db80408fb4a9b96e8393b762" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">17.5</ix:nonFraction> million if Roche advances a medicine under this collaboration.</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_efae3e04708b4937bacd7fa2bb5963f7" contextRef="c20131231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_872b6a5c29be484ca3beb5fa683f1784" contextRef="c20131231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">30</ix:nonFraction>
    million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation.
    We recognized revenue for our R&amp;D services performance obligation over our period of performance, which ended in 2017.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance
    obligation. We recognized each of these payments in full in the respective period in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In 2021, Roche decided to
    discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest HD based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded independent data monitoring committee, or iDMC.</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2023, Roche initiated the Phase 2, GENERATION HD2, study of tominersen in patients with prodromal or early manifest HD. Roche is
    focusing on early-stage and younger patients based on the post-hoc analyses from the GENERATION HD1 study that suggested tominersen may benefit these patient groups. We do not have any remaining performance obligations related to tominersen under this
    collaboration with Roche; however, we can still earn additional payments and royalties as Roche advances tominersen.</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RNA-Targeting Medicines for Alzheimer&#8217;s Disease and Huntington&#8217;s Disease</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2023, we entered into an agreement with Roche to develop <ix:nonFraction name="ions:NumberOfEarlyStagePrograms" id="Fact_9c3e4ea93aaf4a3bb05b35153d252556" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> undisclosed early-stage programs for RNA-targeting investigational medicines for the treatment of AD and HD. Under the agreement, we are responsible for advancing the <ix:nonFraction name="ions:NumberOfEarlyStagePrograms" id="Fact_2fe613bdfb1c49db987a5988045d8b95" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> programs through preclinical studies and Roche is responsible for clinical development, manufacturing and commercialization of the medicines if they
    receive regulatory approval.</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_7664254b686241a0b11ebc9ea18d163f" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">625</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_bf3f3e668d184752b5747be4d075c0af" contextRef="c20231001to20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million upfront payment, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_aa2e94aa8792409880dcb3db6ed96c21" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">167</ix:nonFraction> million in development milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_c439b36908144ae7b03553338428316e" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">398</ix:nonFraction>
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales. From inception through December 31, 2024, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_1a413e3c07c4442cb7fe10585f566939" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million in payments under this collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_c5283e859d7c49818334cf7739246fb6" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.5</ix:nonFraction> million if we advance a medicine under this collaboration.</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_323098af4da04086b03a3676e1b17c62" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> performance
    obligations under this new agreement, comprised of R&amp;D services for each of the <ix:nonFraction name="ions:NumberOfEarlyStagePrograms" id="Fact_4910e794f96649e2841a4bcb84ac292b" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> separate programs. We determined the transaction price
    to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_9b42b643057148369520d4bc807f7d5d" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million upfront payment we received in the fourth quarter 2023. We allocated the transaction price based on the estimated
    stand-alone selling price of each performance obligation as follows:</div>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_dbb92ada6f884b8a95d253549dccc2dc" contextRef="c20231231_ProductOrServiceAxis_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">45</ix:nonFraction> million for the R&amp;D services for the investigational
            medicine for AD; and</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</span><ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_a47e2a76c57e4695b2daade551ea224c" contextRef="c20231231_ProductOrServiceAxis_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the R&amp;D services for t</span>he investigational medicine for HD.</div>
        </td>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-26</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are recognizing revenue for our R&amp;D services
      performance obligations as we perform services based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations. </span>We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> completed our performance obligation for the investigational medicine for AD in June 2024. We currently estimate we will satisfy our performance obligation for the investigational medicine HD at the end of the research term of
      July 2025.</span></div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Roche (in thousands, except percentage amounts):</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Roche</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fb8913807e664ded9db727de95b93bfc" contextRef="c20240101to20241231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">39,871</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_43d5265cf6164fce9ca88f18b5897dc3" contextRef="c20230101to20231231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">48,838</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_20872827ad6c4817bcf759078e23498f" contextRef="c20220101to20221231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">67,202</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_50cff48cda6946bc87457fee3925e81c" contextRef="c20240101to20241231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">6</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_cf5ca05dc07c4448bdda2353f8ed8769" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">6</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_6490dfcad60e494083f50ae6646f73e4" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">11</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_5ff4d7b8efd14d4a81981ea0cfa0cf58" contextRef="c20241231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_a38902f403274142aedd7c7ed42e8214" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">36.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, from our relationship with Roche.</span></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Commercialization Partnerships</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Otsuka</div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2023, we entered into an agreement with Otsuka Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe.
    In the second quarter of 2024, we expanded the agreement to include commercialization rights for donidalorsen in the Asia-Pacific region. As a result, we received a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_9f560fd7e08546f0b11bc9e96dee2da9" contextRef="c20240401to20240630_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction> million upfront payment from Otsuka. We are responsible for the ongoing development of donidalorsen. We retained the rights to commercialize donidalorsen in the U.S. and in the rest of the world, assuming regulatory
    approval.</div>
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  <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17164" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17165">
<div><br/>
  </div>
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  <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17165" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17166">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of this collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_83e4f69e2fa64d648c05bebd72b158cb" contextRef="c20241231_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">290</ix:nonFraction> million, which is comprised of $<ix:nonFraction name="ions:MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" id="Fact_8a8d9e182b6846d8aa9b4ac6ec87b7b0" contextRef="c20241231_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">85</ix:nonFraction> million in upfront payments, up to
    $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_1475c224f3c9433097c24ab20e813634" contextRef="c20241231_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction> million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_4964ef3fe3244ce3a91629a9af0e6fac" contextRef="c20241231_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">140</ix:nonFraction> million in sales milestone payments. In addition, we are eligible to receive tiered royalties up to <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_d5b20d1cba704a8cb0fffbe29fba3f2b" contextRef="c20240101to20241231_RangeAxis_MaximumMember_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">30</ix:nonFraction> percent
    on net sales. In the fourth quarter of 2024, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e5955679b2b04e85b81a69cdea888ab7" contextRef="c20241001to20241231_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction> million milestone payment from Otsuka when the EMA accepted our Marketing
    Authorization Application, or MAA, filing for donidalorsen in the European Union, or EU. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_c1d2152e2c604418a9c3c7376ad14171" contextRef="c20241231_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction> million if the
    European Commission approves donidalorsen under this collaboration.</div>
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  <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17166" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17167">
<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_27fb7f4e535a470eaab5dc07fee5038a" contextRef="c20231231_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> performance
    obligations under this agreement, comprised of our license of donidalorsen to Otsuka and R&amp;D services for donidalorsen. We determined the transaction price to be $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_ebadc349803b440ebdc2ca77c18844a0" contextRef="c20231231_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">85</ix:nonFraction> million, comprised of the following:</div>
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<div><br/>
  </div>
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  <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17169" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17170">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_c3b4dd0099644e2b9bb90fe6c5e76d65" contextRef="c20230101to20231231_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction> million from the upfront payment we received in 2023; and</div>
        </td>

  </tr>


</table>
</ix:continuation>
  <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17170" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17171">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_d4f3c79febcb4a109e8ebaba69dd5452" contextRef="c20240101to20241231_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction> million from the upfront payment we received in 2024.</div>
        </td>

  </tr>


</table>
</ix:continuation>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:</div>
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<div><br/>
  </div>
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  <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17174" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17175">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_bc5e5327115f4deea2ae75dc63832c93" contextRef="c20231231_ProductOrServiceAxis_LicenseOfDonidalorsenMember_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">73.5</ix:nonFraction> million for the license of donidalorsen; and</div>
        </td>

  </tr>


</table>
</ix:continuation>
  <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17175" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17176">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_78ea72b1d4a54c649943487acf03c123" contextRef="c20231231_ProductOrServiceAxis_ResearchAndDevelopmentServicesForDonidalorsenMember_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">11.5</ix:nonFraction> million for the R&amp;D services for donidalorsen.</div>
        </td>

  </tr>


</table>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our
    performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligations in March 2026.</div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2024, we entered into an agreement with Otsuka to commercialize ulefnersen worldwide. We are responsible for the ongoing
    development of ulefnersen.</div>
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<div><br/>
  </div>
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  <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17181" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17182">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From inception through December 31, 2024,
    we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_8bacb479b10f4a519b6f9f0b60fdf84f" contextRef="c20241231_TypeOfArrangementAxis_OtsukaCollaborationDonidalorsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">95</ix:nonFraction> million in payments under these collaborations.</div>
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<div><br/>
  </div>
</ix:continuation></div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-27</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the year ended December 31, 2024, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amount):</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Otsuka</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_876ed76e4d5d4082bb8489afed17194d" contextRef="c20240101to20241231_TypeOfArrangementAxis_OtsukaCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">46,856</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_148faca39ccc4924bb9f9f064b697f23" contextRef="c20230101to20231231_TypeOfArrangementAxis_OtsukaCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">56,480</ix:nonFraction></div>
        </td>

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          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_7324809979874e408c6a9594878a79b4" contextRef="c20240101to20241231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_OtsukaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">7</ix:nonFraction></div>
        </td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_513f190308d54fe9a66fa71249bdcb78" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_OtsukaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">7</ix:nonFraction></div>
        </td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_ab2db9a4c2814c19ba0f374053b31f7e" contextRef="c20241231_TypeOfArrangementAxis_OtsukaCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_7175d160c23e44fe8c1490530e0cd4cc" contextRef="c20231231_TypeOfArrangementAxis_OtsukaCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, from our relationship with Otsuka.</span></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PTC Therapeutics</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2018, we entered into an exclusive license agreement with
      PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries. Under the license agreement, we are eligible to receive royalties from PTC in the mid-</span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" id="Fact_570d071a48d248dbb4cd460b720cd572" contextRef="c20240101to20241231_TypeOfArrangementAxis_PtcTherapeuticsCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> range on net sales for each medicine. </span>In December 2021 and September 2023, we
    started receiving royalties from PTC for TEGSEDI and WAYLIVRA sales, respectively<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Swedish Orphan Biovitrum AB (Sobi)</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2021, we began commercializing TEGSEDI and WAYLIVRA in
      Europe and TEGSEDI in North America through distribution agreements with Sobi. </span>Under our distribution agreements, Sobi is responsible for commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. We are
    responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. Under our agreements with Sobi, Sobi does not generally have a right of return. We recognize as revenue the price Sobi
    pays us for the inventory when we deliver the finished goods inventory to Sobi. In addition, we earn a distribution fee on net sales from Sobi for each medicine.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2023, our distribution agreement for TEGSEDI in North America was terminated and Sobi began transitioning responsibilities to
    us. Following the transition, we discontinued TEGSEDI in North America in 2024. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">During the years ended December 31, 2024, 2023 and 2022, we earned nominal revenue from our
      distribution agreement with Sobi for TEGSEDI in North America.</span></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Technology Enhancement Collaborations</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bicycle Therapeutics</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2020, we entered into a collaboration agreement with Bicycle and <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">obtained an option to license its peptide technology that we expect can expand our LICA platform to target both skeletal and cardiac muscle, and potentially deliver medicines across the blood brain barrier</span>. In 2021, we paid $<ix:nonFraction name="ions:PaymentsMadeUnderCollaborationAgreement" id="Fact_5f30af4db40c410198d4adf0cf56a2ac" contextRef="c20210101to20211231_TypeOfArrangementAxis_BicycleCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">42</ix:nonFraction> million when we exercised our option to license Bicycle&#8217;s technology, which included an equity investment in Bicycle. As part of our stock purchase, we
    entered into a lockup agreement with Bicycle that restricted our ability to trade our Bicycle shares for <ix:nonNumeric name="ions:LockUpAgreementTermOfTradingRestriction" id="Fact_3b6f7ff3760d482699aca63514d611a3" contextRef="c20240101to20241231_TypeOfArrangementAxis_BicycleCollaborationMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric>. In 2021, we recorded a $<ix:nonFraction name="ions:InvestmentInEquitySecuritiesFvNi" id="Fact_c4984ca504f041ad810726dda263687c" contextRef="c20210101to20211231_TypeOfArrangementAxis_BicycleCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.2</ix:nonFraction> million equity investment for the shares we received in Bicycle. We recognized the remaining $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpense" id="Fact_f54d6f5ead044550b599ce90b22d6d17" contextRef="c20210101to20211231_TypeOfArrangementAxis_BicycleCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">34.8</ix:nonFraction> million as R&amp;D expense in 2021. W<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e will pay Bicycle milestone payments and royalties that are
      contingent on the achievement of certain development, regulatory and sales events.</span></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Metagenomi</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, we entered into a collaboration and license agreement with Metagenomi to research, develop and commercialize investigational
    medicines for up to <ix:nonFraction name="ions:NumberOfTargetsToBeResearchedDevelopedAndCommercialized" id="Fact_18af6039c1e84b2ea2c0a807341f97ff" contextRef="c20221231_TypeOfArrangementAxis_MetagenomiLicenseAgreementMember" unitRef="U014" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> initial genetic targets, and, upon the achievement of certain development milestones, <ix:nonFraction name="ions:NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized" id="Fact_6871a5f8bed24372ba3c40c2e27a51f5" contextRef="c20221231_TypeOfArrangementAxis_MetagenomiLicenseAgreementMember" unitRef="U014" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> additional genetic targets using gene editing technologies. As a result, we paid $<ix:nonFraction name="ions:PaymentToLicenseTechnology" id="Fact_537c87b66c264e69b2abf8afc8e75f50" contextRef="c20220101to20221231_TypeOfArrangementAxis_MetagenomiLicenseAgreementMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">80</ix:nonFraction> million to license Metagenomi&#8217;s technologies and will pay Metagenomi certain fees for the selection of genetic targets. We recorded the $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost" id="Fact_e055474b91a641ecbda62b2a56a15444" contextRef="c20220101to20221231_TypeOfArrangementAxis_MetagenomiLicenseAgreementMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">80</ix:nonFraction> million payment as R&amp;D expense in 2022 upon receiving a license from Metagenomi for intellectual property that is in research with no current alternate use. In addition, we
    will pay Metagenomi milestone payments and royalties that are contingent on the achievement of certain development, regulatory and sales events. We will also reimburse Metagenomi for certain of its costs in conducting its research and drug discovery
    activities under the collaboration.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Other Agreements</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Alnylam Pharmaceuticals, Inc.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of our agreement with Alnylam, we co-exclusively (with ourselves) licensed to Alnylam our patent estate relating to
      antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics, with Alnylam having the exclusive right to grant platform sublicenses for double-stranded RNAi. In exchange for such rights, we are eligible to earn
      a technology access fee, participate in fees from Alnylam&#8217;s partnering programs and earn future milestone and royalty payments from Alnylam. We retained exclusive rights to our patents for single-stranded antisense therapeutics and for a limited
      number of double-stranded RNAi therapeutic targets and all rights to single-stranded RNAi, or ssRNAi, therapeutics. In turn, Alnylam nonexclusively licensed to us its patent estate relating to antisense motifs and mechanisms and oligonucleotide
      chemistry to research, develop and commercialize single-stranded antisense therapeutics, ssRNAi therapeutics, and to research double-stranded RNAi compounds. We also received a license to develop and commercialize double-stranded RNAi therapeutics
      targeting a limited number of therapeutic targets on a nonexclusive basis. Additionally, in 2015, we and Alnylam entered into an alliance in which we cross-licensed intellectual property. Under this alliance, we and Alnylam each obtained exclusive
      license rights to <ix:nonFraction name="ions:NumberOfTherapeuticPrograms" id="Fact_b59f89497d794a21b1c2df7b377e99c3" contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> therapeutic programs. Alnylam granted us an exclusive, royalty-bearing license to its chemistry, RNA targeting
      mechanism and target-specific intellectual property for oligonucleotides against <ix:nonFraction name="ions:NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" id="Fact_70e205c126b840cea61764ddc5de1617" contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U014" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> targets, including FXI and Apo(a) and <ix:nonFraction name="ions:NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" id="Fact_c487e303480e4ab0959ebfea8f93a143" contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U014" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> other targets. In exchange, we granted Alnylam an exclusive, royalty-bearing license to our chemistry, RNA targeting mechanism and target-specific
      intellectual property for oligonucleotides against <ix:nonFraction name="ions:NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" id="Fact_a45941bb66ed4a98a86c4ba3cf2c4f42" contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U014" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> other targets. Alnylam also granted us a royalty-bearing, non-exclusive license to new
      platform technology arising from May 2014 through April 2019 for single-stranded antisense therapeutics. In turn, we granted Alnylam a royalty-bearing, non-exclusive license to new platform technology arising from May 2014 through April 2019 for
      double-stranded RNAi therapeutics.</div>
</ix:continuation>
  </div>

  <div><ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17214" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17215">
<div><br/>
  </div>
</ix:continuation></div>

  <div>
    <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17215" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17216"><ix:nonNumeric name="us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" id="Text_0f88f578e1cc4bc5928904be72a89aac" contextRef="c20240101to20241231_TypeOfArrangementAxis_AlnylamPharmaceuticalsIncMember" escape="true" continuedAt="Text_728cf3b6d444402782f97306943034ce1">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022, we earned the following revenue from our relationship with Alnylam (in thousands, except percentage amounts):</div>
</ix:nonNumeric></ix:continuation>
    <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17216" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17217"><ix:continuation id="Text_728cf3b6d444402782f97306943034ce1" continuedAt="Text_728cf3b6d444402782f97306943034ce2">
<div><br/>
    </div>
</ix:continuation></ix:continuation>
  </div>
<div><ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17217" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17218"><ix:continuation id="Text_728cf3b6d444402782f97306943034ce2">
<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Alnylam</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_45285d7fd8354da4a078a4a11aba04ee" contextRef="c20240101to20241231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,110</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_234485bc14344d888b7bed969bbbb34c" contextRef="c20230101to20231231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,426</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_bce450e4b0344107ac0e55460c018791" contextRef="c20220101to20221231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">21,389</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_2cfe3b7062dc4a9cb5ee360d01476480" contextRef="c20240101to20241231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_ab0a985934234f8bb07ff855cb4f906d" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">4</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_bd1c6a81db934c3e9265b1322ef276f8" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">4</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>

  <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17218" continuedAt="Text_384847e2c2914aa4ad548d68ae62fd17219">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_384847e2c2914aa4ad548d68ae62fd17219">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_87589be5c6de472fa7c2f37215199412" contextRef="c20231231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_12c9599416c543e7890f0ee3f45418ed" contextRef="c20241231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t have any
    deferred revenue from our relationship with Alnylam at December 31, 2024 and 2023.</div>
</ix:continuation></div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:InvestmentTextBlock" id="Text_9571e0c61df44815a452af9dc71349ef" contextRef="c20240101to20241231" escape="true" continuedAt="Text_645adecc88bb417cb9a85ca88a9e12571">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5. Investments</div>
</ix:nonNumeric>

  <ix:continuation id="Text_645adecc88bb417cb9a85ca88a9e12571" continuedAt="Text_645adecc88bb417cb9a85ca88a9e12572">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_645adecc88bb417cb9a85ca88a9e12572" continuedAt="Text_645adecc88bb417cb9a85ca88a9e12573"><ix:nonNumeric name="us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock" id="Text_df6d78f5b0db4f2293f255a3abc4674a" contextRef="c20240101to20241231" escape="true" continuedAt="Text_4784f0d2935d42e399cb3c9c997ec89d1">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2024:</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_645adecc88bb417cb9a85ca88a9e12573" continuedAt="Text_645adecc88bb417cb9a85ca88a9e12574"><ix:continuation id="Text_4784f0d2935d42e399cb3c9c997ec89d1" continuedAt="Text_4784f0d2935d42e399cb3c9c997ec89d2">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_645adecc88bb417cb9a85ca88a9e12574" continuedAt="Text_645adecc88bb417cb9a85ca88a9e12575"><ix:continuation id="Text_4784f0d2935d42e399cb3c9c997ec89d2">
<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_a0389bbbc04d444aa9945a16f2f77b47" contextRef="c20240101to20241231" format="ixt-sec:durwordsen">One year</ix:nonNumeric></span>
            or less</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" id="Fact_e1a84f7ba1234915827448c633c10e96" contextRef="c20241231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">69</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_a9a809b245674eb5912c14df728dc0f0" contextRef="c20240101to20241231" format="ixt-sec:durwordsen">one year</ix:nonNumeric></span>
            but within <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_d1dd3aa1c3444cc8babea1f02c42cb74" contextRef="c20240101to20241231" format="ixt-sec:durwordsen">two years</ix:nonNumeric></span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" id="Fact_54f16a3082454b16a1368f8660393627" contextRef="c20241231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">24</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_649df9025a904bcfad6dc6ab6bd4c304" contextRef="c20240101to20241231" format="ixt-sec:durwordsen">two years</ix:nonNumeric></span>
            but within <span style="text-indent: 0pt;"><span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30">three and a half years</span></span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" id="Fact_d60e9c8e586b428c886b9d9653ac0f6e" contextRef="c20241231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">7</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" id="Fact_298fc5ad20a2442399af2cd8e8215ece" contextRef="c20241231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As illustrated above, at December 31, 2024,
    <ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="Fact_971b070bcf6846b8970847cdbaef1457" contextRef="c20241231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">93</ix:nonFraction> percent of our available-for-sale securities had a maturity of less than <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_e4aa3be8fcd040d0bcd0def824af337d" contextRef="c20240101to20241231" format="ixt-sec:durwordsen">two years</ix:nonNumeric>.</div>
</ix:continuation>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these
    securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date.</div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We invest in debt securities with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp;
    Poor&#8217;s, Moody&#8217;s or Fitch, respectively.</div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At December 31, 2024, we had an ownership interest of less than 20 percent </span>in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_c487d989afb240aaae9be0536d4b8656" contextRef="c20241231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">seven</ix:nonFraction>
    private companies and <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_cc8fa179d30548a7b52fcdc75fe7eeee" contextRef="c20241231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> public companies with which we conduct business<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div><br/>
  </div>
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  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-29</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
<div><ix:continuation id="Text_645adecc88bb417cb9a85ca88a9e125714" continuedAt="Text_645adecc88bb417cb9a85ca88a9e125715"><ix:nonNumeric name="us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock" id="Text_8334d44cad3443a9ab4f38e658200dff" contextRef="c20240101to20241231" escape="true" continuedAt="Text_95eab7985baf4e1a8996d5a46384f2a61">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>
</ix:nonNumeric></ix:continuation>

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<div><br/>
  </div>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortized</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2024</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_bc9e70d55b674cc9b6be541478de94e8" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">593,810</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_0c24393396f14a5fadd7e6d9dd062834" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">487</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_615e6981ef5c43e4afa6a302941c0754" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">240</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_0a185c2049a6469e81e8e4df671bb2f5" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">594,057</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_c9d17af33c554c64ac738dfbdb48494c" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">143,647</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_e61b3c1e7a7a45d7a7ce7d512404dfea" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">287</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_8cd5ebaff4ff47b59a6f49c94f90f5e4" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">39</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_dc66d2f463f54767abee4fc4f62595f6" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">143,895</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_f00bcd75b4b842ec98fdc045c48c2576" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">657,285</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_d6b1880a34fc425f848f593694e21d3b" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">825</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_52ee12eba4604cd6beb6d916ef074d49" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">120</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_93f61f2dcaf249fe8c2941b0bedb2ad6" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">657,990</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_f17e37bd45aa4fdbae4827a34aa7dac9" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,516</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_8da02b683fe94c99ae3334fe0583bcbf" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_f5548b5e22d64358b14bff13c4cde745" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_5215ece6e8674be582ac13fad8e0e02f" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,524</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_06b37f3d76b24645b428aed40ef7519d" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,402,258</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_868aecd154b3411fad39ee7f067ae085" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,607</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_27ce74de3a8d48ed86f8ce84429f7f33" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">399</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_7cbbbf68a23c4d05acea3eb703650eb7" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,403,466</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_68c90e44ae7142faa5c935422fe6ca01" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">439,561</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_0ecb6c8cead3473f9be6b9fc2b15d79f" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">723</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_4f2e99491c92483882c5013894e5a3b4" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,275</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_8078467ba1d947589f274b1470ccc8c7" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">438,009</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_e4c79d28e0dd438c896e0c5148cdbae0" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">65,255</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_c3fb53b35b5e4f0a801fb17377bbe452" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">137</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_f20247b6d2f84ccbbb1dbab68b9cd3d6" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">289</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_a656c02b450b4ae39000dbd1d10a2d67" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">65,103</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_160b2612c5ff403daa0b23ecdd2866db" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">149,086</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_b1272ac8ac42497ba65853e630ea020a" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">124</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_803581e2009f4b95bf2af6ab10413c74" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">476</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_32fdcfaa188c4467a9bc336b98ee4765" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">148,734</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_8a1059702cb04a949b4c23a6d5766e37" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">698</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_a2e7b36fcc8649dfba2e116fe7816c10" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_1ec4eaa0e3154ac181fd8ade92ef1bc6" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_227ebf68b6004881937fcc9c29fd6b90" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">696</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_b71803caad4d4886ad41f6bbc5e209f5" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">654,600</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_8a0a49d9cc1e4c129249d0be27e415f2" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">984</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_0ca92b9c73b2492aadcfbe4f82a50cb4" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,042</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_91167061047b48f4b8610c1a21447584" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">652,542</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_a5e37551797746d7832fc5653898ad64" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,056,858</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_5784263002924b25aff1cb14f626bf7f" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,591</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_7654b51ce0a5448fa1c5723b77e4a3cd" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,441</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_fb3ebfc0325446129501360d15bf62ff" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,056,008</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (2)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_cef09f69ddec4b3dabee2b4ce3e2377b" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_3f654be6d96e41e4b4713c77ccf1c8e3" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">26</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_3d2a388042994347ab5102d669861a7d" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,660</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_2d87969d9ae34d49b910e43cebb1d676" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,263</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Privately held equity securities included in deposits and other assets (3)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_9ebd36323e384809b15acae0a3551932" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">23,115</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_aed73c2c4de9479b940ffa549e9fedd0" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,001</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_1f1394dc79044e9197f515e0b7bca042" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,093</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_acab1218ec2e41199e1b320128741143" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">41,023</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_1f62fdc7a62342f68a33d50b3bde0a58" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">35,012</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_c2b1f14b00d941b6b317ee97742c8d96" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,027</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_9d1928afc7224324b66d25fddff38253" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">13,753</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_594521b1bd6241bea5eaec95f58271c0" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">46,286</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;">
          <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_afee4ce7ef954363a1010e810f1ae960" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,091,870</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_a346c4f456874316909407a757ecc1b7" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,618</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_0bd6c064edff43c09905fc28e289473e" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,194</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_f35d561e61484f2295cadeeb2d03bdbd" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,102,294</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>


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</ix:continuation></ix:continuation>
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<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_645adecc88bb417cb9a85ca88a9e125718" continuedAt="Text_645adecc88bb417cb9a85ca88a9e125719"><ix:continuation id="Text_95eab7985baf4e1a8996d5a46384f2a64" continuedAt="Text_95eab7985baf4e1a8996d5a46384f2a65">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortized</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2023</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_8ea119980dc64034994a6b7ad86f848c" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">559,967</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_6df2fbe2752e4bd0bb77abf8abe0ae29" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">157</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_73421ff544c5487b9e733e95b060b569" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,625</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_c85091a5a55a45a881f09b4c8c70a29c" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">557,499</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_da1b311c89004135b55ecee7befa549d" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">224,711</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_6c6ca7c3257b46848b5da442e9d2b424" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">64</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_f8696120bd5749f081186004728dcfec" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">611</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_ba83c8acf52443779871f0f7f21e0f69" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">224,164</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_267f46317f0b40caa2f037611c038a1e" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">513,784</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_2d25c6a792494377addd272a5b8dded6" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">152</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_f56cc4d0d90d4e7fbb8f72585969858c" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,889</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_0c7a5d61dae34de8a30b14b8802b8785" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">512,047</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_2665cd241db44217ad8643b9ae2a63da" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,757</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_5244a18f7849464e8277366dd5790037" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">42</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_703babc31466440681b56330914ed672" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">113</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_8732df0d6eac436fa8da11aab067289a" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,686</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_f91f4bf7895e4255b6fb1606547e04c4" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,316,219</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_58f014330e0d46f68ac56681d9bcc775" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">415</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_4d687e924d2549c292e3b98c471a8b1c" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,238</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_5b653caa5875494f883c075c43b1bf5c" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,311,396</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_90b66da8071a4a14ae79ae20e35a4725" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">243,151</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_6969869c8ab34390a5923698c47c72bb" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,270</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_fa5a358807714f81a4468c02e061a381" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">692</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_c8341442a25e450b8c2a53f28afa5bbb" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">243,729</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_627bd1dd191a4e2aa0ffcac3c093515e" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">110,138</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_de7b01c6aeff4c67be7342b578227fe7" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">547</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_6dd609ef5c9d4c5abd47201f2f3c3971" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">21</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_01ade62c43ae4d1d9d121b813ab06110" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">110,664</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_1a4e37f7b16f498caa99b193ac3977d1" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">294,873</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_9e774f36b3824b5da1f596ef542f70e8" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,239</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_fcf3826f90e44039b289f8286697222d" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">480</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_3834f60c806146fdb57604df4ca44d5f" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">295,632</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_3b50fc36268c472c83543a498f74c6a3" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,466</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_3cc6fe9c6c684eabbb359b5b57a83381" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_f9f79be238454b459039ee2cf29f6635" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_285a93f311de42a8b8b01192c7d0cee6" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,469</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_be05404e83c643348777fa91b0e1b9ba" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">651,628</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_80c5acbabb8c4f0bb30f07636779a6ef" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,063</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_2d2b1cb797c643148d37d334e933eeb2" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,197</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_2bbc29a667a94cb99ff6c9f040ebeea6" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">653,494</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_8caafd476a3541b9aef7c098cc041e94" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,967,847</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_609132a66d2f4130b140a88c2fb0c89d" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,478</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_b09e4761e6054b25a622ed40b8db284e" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,435</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_4de7d9b3be6d447db4b3c3fe0b8f036b" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,964,890</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (2)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_ddb646a5d0f1447b92caf9f07a627fcd" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_88ed4a2745c54e14a622755a003ef7d5" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">236</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_b4cdd38512ef47d9b5d3df0de25143e1" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,832</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_c71d4b805e374b9696b1907d0c3b8708" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,301</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Privately held equity securities included in deposits and other assets (3)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_fd07a2a1606f48d78bc5fb285d90a137" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">23,115</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_f166a5e138d3457b82d04bfee0b2aaa8" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,001</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_377148fd543d4bcd9b069e1883f63342" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,125</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_250e88ec455a48818d6c542e743f1801" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">42,991</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_8cbb173fbf424d2cae5761cfe86aa386" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">35,012</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_c7bf32577ac44c999892ccbf176d194e" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,237</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_7050ac2adf394b31b986c11c8b0618f6" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,957</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_b3f9adef6e924b3c91c0bc0573208fed" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,292</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;">
          <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_c31aca2dbed748588049458efeea09a7" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,002,859</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_c255d1502e344319b6e94f49f85ceeb8" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,715</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_442681fd5f144b86afca5af925fffb02" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,392</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_59bf550c30564d83b459e349c7ec3c12" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,014,182</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_88fe67a8cca841eaa8660167eec626fe" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Includes investments classified as cash equivalents in our consolidated
            balance sheets.</ix:footnote></div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_33f87045331d4d29a03153170558d0a1" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Our publicly traded equity securities are included in other current
            assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2024, we recorded a $<ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_97381c7c87c2484fa19e43717dc354ca" contextRef="c20240101to20241231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.0</ix:nonFraction> million net <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">unrealized loss in our consolidated statement of
              operations related to changes in the fair value of our investments in publicly traded companies.</span></ix:footnote></div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_92f3ab0ee45a44b9baf44a6e4c6792b4" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at</span> cost minus impairments, plus or minus changes resulting from observable price changes in
            orderly transactions for the identical or similar investment of the same issuer, which are Level 3 inputs. In the year ended December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recorded a $</span><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_21be0b159b95436b92c2237984c9ce9d" contextRef="c20240101to20241231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.0</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million net unrealized loss in our consolidated statements of operations related to observable price changes of our investments in privately held companies.</span></ix:footnote></div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-30</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our investments we considered to be temporarily impaired at&#160;</span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;(in thousands, except for number of investments):</span></div>
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Temporary</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impairment</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_f4a5c25e37b543f7932cc0d01427eb2b" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U015" decimals="0" scale="0" format="ixt:num-dot-decimal">274</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_8e48e186979f4b918d2edbccb3d5b01c" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">488,949</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_7fdf176baf4d4864ac3a9538410eb63b" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,463</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_f35695329a0a47938d27089c6693459f" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,713</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_7e9108673c6f481cbe3b9965b6cfd9cb" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">52</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_8fb2ae4a1ec045fa9a3e85eb73fd7579" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">516,662</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_324d1ca3c5b04a21a80ffb6c2a84d43e" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,515</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_470fc8ee60a84e25b6fc08a2cbb85990" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U015" decimals="0" scale="0" format="ixt:num-dot-decimal">30</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_aeff41705ae349b29427d35a8d443bf7" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">67,854</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_8fba36c97e7d4a80a1ae60c439a9af03" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">328</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_f657b8c8ce234a3daf422cd98844996b" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_125efbdc4abf453ea61824f7f8dfcbdf" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_2fbf57c2ffa245f294b609d611c85a62" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">67,854</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_cbfbf344402746efbb0dcac0962c7ce3" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">328</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_dbb0a900723b4e209ffa74a517efd053" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U015" decimals="0" scale="0" format="ixt:num-dot-decimal">38</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_39c3036d6aee4e01b4a3ae672c4b0896" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">252,926</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_40dcd840d1a240968fdca65e541675b7" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">503</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_f5da7f349913446f8c02b0bf6053fd09" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">24,173</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_9c658483c775407ba8d359cb397e54eb" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">277,099</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_c185480eb0914a3295c76692e3bcadd1" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">596</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_71c2fda61dc846298eeff9b0ca38115c" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U015" decimals="0" scale="0" format="ixt:num-dot-decimal">3</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_6990d89425474cfc9c4b8bf0d8cf7439" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">643</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_4a48d7c90c5a4a0bbe2ae5be47316023" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_a28ea3274df5428e98f07b9d17b49fab" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">129</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_687e88a52c8446078d869df0c183470d" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_c17115e0327d4b7ca7c6e3aadbaaf14f" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">772</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_8c469d84d7df46f7a259af6e5d56319a" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_f0b189d5bee24df980858e09a9b29c10" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U015" decimals="0" scale="0" format="ixt:num-dot-decimal">1</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_c046183327974883beff72c6ba6c6076" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">696</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_44e570e47441456ca88d7ceb810965a4" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_62b1de54e6344c3db11754e33adf38fc" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_934cae03aef541049e55a54748207564" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_2f81d189e00249c78b393869e29708dc" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">696</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_8c783f593cb74132bf1d8e5249946459" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_c5a13e110d15472bb7209a893f75760c" contextRef="c20241231" unitRef="U015" decimals="0" scale="0" format="ixt:num-dot-decimal">346</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_bcffdf58f44a4915b5c47f23299cb0a4" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">811,068</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_258d034cad9c41d5818f3ff1c5e9ac54" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,296</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_8d829588e22141b8a62fed91d7622b5e" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">52,015</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_36b440f266f44cfa9a6ffb88f94ffc3f" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">145</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_29ce681916874294a263914fba442f04" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">863,083</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_c6330165fcf44008a4bcbadea16125b1" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,441</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_645adecc88bb417cb9a85ca88a9e125729" continuedAt="Text_645adecc88bb417cb9a85ca88a9e125730">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_645adecc88bb417cb9a85ca88a9e125730">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates
    since purchase rather than underlying credit deterioration for any of the issuers. We believe it is more likely than not that we will be able to hold our debt securities with declines in value to maturity. Therefore, we intend to hold these securities
    to maturity and anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</div>
</ix:continuation></div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:FairValueDisclosuresTextBlock" id="Text_a080c2e549ed48798336fbfa516a174a" contextRef="c20240101to20241231" escape="true" continuedAt="Text_206d4d3192b74196a010ab5c40238ce81">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6. Fair Value Measurements</div>
</ix:nonNumeric>

  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce81" continuedAt="Text_206d4d3192b74196a010ab5c40238ce82">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce82" continuedAt="Text_206d4d3192b74196a010ab5c40238ce83"><ix:nonNumeric name="us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock" id="Text_161f38ed596b48a19876a8584a322dc2" contextRef="c20240101to20241231" escape="true" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b1">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at December 31, 2024 and 2023&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective
    securities&#8217; fair value (in thousands):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce83" continuedAt="Text_206d4d3192b74196a010ab5c40238ce84"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b1" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b2">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce84" continuedAt="Text_206d4d3192b74196a010ab5c40238ce85"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b2" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b3">
<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_436883975bf3468b92c09cc61e03fa41" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">180,445</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_79dfa1d423f642cea572a5bb9c411e6e" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">180,445</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_65c74896addd4b7890c68f56ab5c5f70" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_bd40b54476544609af8d4027bb17852a" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,032,066</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_47015bf7b4364a728c529aec5394713b" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_ce2106e4180b41eb85df7504ba1e6268" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,032,066</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_b9f55a2040604cca8871949edbe9c0ea" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">208,998</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_86e4aa20eea74f8787ba658ab420d933" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_f735c515b82742aeba74bdbab4e4e4a5" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">208,998</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_f597ef484dc849b3869c0b24b7e47ca0" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">806,724</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_d4426d3c42f14b8c87105791656383d6" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">806,724</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_8508dcfab1e4444dab865f21eafaac04" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,524</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_85146eb5ada740ee9a53b19db08fdc47" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_a2f79fbed84d4f169900f21d26a0c14b" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,524</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (2)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_1d0ac70971b04d78ac95509b498777cf" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">696</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_5802ef0a02174c3ba604fca048068b08" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_c2e7085e9fff403aaa1a1010acb4f49f" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">696</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (3)</div>
          </div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_3a7b94ae1575483d99cdff167336737c" contextRef="c20241231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,263</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_dcbce3ea27dc430f9082c8d96ba2c86b" contextRef="c20241231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,263</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_9b2894878d734371a537f270d1142205" contextRef="c20241231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_41aa8ca715a246c6ab132f68d33110c2" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,241,716</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_14262b51a03546e9864249ccb9ca4a20" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">992,432</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_8134fdf4a60f4810b009f807fc4ce04e" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,249,284</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce85" continuedAt="Text_206d4d3192b74196a010ab5c40238ce86"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b3" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b4">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce86" continuedAt="Text_206d4d3192b74196a010ab5c40238ce87"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b4" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b5">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_6f9a8b7bb0274b6aa4ebdbfd8ec1cda4" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">185,424</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_d022e13f5bfc44a485ff5fc107b87349" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">185,424</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_0dd4548c72224cd6975d2b0c28babec7" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (4)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_15e5c1c8e15b4ec985dcee227484669f" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">801,228</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_fb9b7215206045289d5ac989482b34ac" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_7b7ffacc071c46e28e5bc02c6cbdf406" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">334,828</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_f00f0183fbdb414bb8ace8c09326de91" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_6bff7c97ac774c11923e8315e813ef18" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">334,828</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_3f43d316784545c8b69beec4e9b1bf54" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">807,679</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_9f168d9ee16e4f3b813f38c507fa28b1" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">807,679</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_0e067bc23c4d4301839ded59e2581b10" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_f4d1d69ba9254d3b8aff137c28df29e2" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">21,155</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_7ea5abb7b7dc46d8b9f0f873e9607020" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_e8c040876cb94663b41bc3252cdfe50f" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">21,155</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (3)</div>
          </div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_37704b09f78f4b92a28ef1c4adab51e6" contextRef="c20231231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,301</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_c115b34d583a44a29382311b1404da7b" contextRef="c20231231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,301</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_8bfd913d5c5c43aeb9ae030ed40f9b2c" contextRef="c20231231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_57c8091a5a114c3c8f6bccd694eb8b0e" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,156,615</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_9efce47d082648b086daa33248918cfb" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">999,404</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_45cbd4a07e9d4ab8b914ee2d30888ee9" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,157,211</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce87" continuedAt="Text_206d4d3192b74196a010ab5c40238ce88"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b5" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b6">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce88" continuedAt="Text_206d4d3192b74196a010ab5c40238ce89"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b6" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b7">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_ad43559c353f456eac7c04729a412d6f" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in cash and cash equivalents in our consolidated balance
            sheets.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce89" continuedAt="Text_206d4d3192b74196a010ab5c40238ce810"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b7" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b8">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce810" continuedAt="Text_206d4d3192b74196a010ab5c40238ce811"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b8" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b9">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_77eb85d4142a44a68a7c6b25a7169d1c" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in short-term investments in our consolidated balance sheets.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce811" continuedAt="Text_206d4d3192b74196a010ab5c40238ce812"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b9" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b10">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce812" continuedAt="Text_206d4d3192b74196a010ab5c40238ce813"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b10" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b11">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_f0e1d58ea08e4b55a4c7703dd1e397d3" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in other current assets in our consolidated balance sheets.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce813" continuedAt="Text_206d4d3192b74196a010ab5c40238ce814"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b11" continuedAt="Text_8e657d7cb2b841b58ae5f0c0598d732b12">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_206d4d3192b74196a010ab5c40238ce814" continuedAt="Text_206d4d3192b74196a010ab5c40238ce815"><ix:continuation id="Text_8e657d7cb2b841b58ae5f0c0598d732b12">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_5618a89e2fcf4ea18d4496f6d55029f1" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_99b5e575cc9b4c04a4aebda207f82f5d" contextRef="c20231231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">33.0</ix:nonFraction> million was included in cash and cash equivalents, with the difference included in short-term investments in our consolidated balance sheets.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-31</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Convertible Notes</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fec8350d2b584c31a556d0714630ce22" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_47cf6f98169049fbac9d864c715e8edb" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes had a fair value of $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_f659cb73d02d4ef08f0df32bb027b149" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">569.3</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_f0e3f2364810404e841460fd9d182b2b" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">612.8</ix:nonFraction> million at December 31, 2024,
    respectively. Our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_555d5fb95d114f2fb6f220a2e2845841" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes, <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b7457058b28145b0867b28e4cdf052b8" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%
    Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_993fb424c7ea4aeca72c8416825c1ae6" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes had a fair value of $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_88db57eb1d7148a894902bfffd9f3f5c" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">661.1</ix:nonFraction>
    million, $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_652e96fb5173482cbf79e70837714c32" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">667.8</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_213c709db7e14a5793454ab709c9bcc4" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">42.4</ix:nonFraction>
    million at December 31, 2023, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are
    Level 2 measurements because the notes do not trade regularly.</div>
</ix:continuation></div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:DebtDisclosureTextBlock" id="Text_1f7799e29d9c4fd5ac2c30d64ad9a625" contextRef="c20240101to20241231" escape="true" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c81">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Long-Term Obligations and Commitments</div>
</ix:nonNumeric>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The carrying value of our long-term obligations was as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
  </div>
</ix:continuation></ix:continuation>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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  <tr>

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            convertible senior notes</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebt" id="Fact_9d8ce4d747b14e70b17d777d1cc23dd4" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">565,026</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebt" id="Fact_76e0c4ca0c534ca589e77e4c976b992c" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">562,285</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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            convertible senior notes</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebt" id="Fact_cc24fb43c0744f1c98325749d3d1c0eb" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">628,535</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet" id="Fact_0d3477713a1c4a8a88765ea8505721f4" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">542,212</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet" id="Fact_0bd1dad24d2643279f4173819bd5adf1" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">513,736</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lease liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseLiability" id="Fact_8f7e7fa2aaf644beafdec103f6046e51" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">178,969</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mortgage debt</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LoansPayableToBank" id="Fact_7526ddee5b884532b24be01e4d495612" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,714</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LoansPayableToBank" id="Fact_1a31cb06bce14608b6b4bc53c537a2e8" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,859</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other obligations</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherLiabilities" id="Fact_4f4ce1cf534445a182bc4dc79c4da3ed" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">43,425</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligations" id="Fact_67f1e8de33db4b3ba71a251d6969a0e4" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,958,781</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligations" id="Fact_0db6c0acf39c4704b8b7fb0682124be0" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,922,943</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: current portion</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:LongTermObligationsCurrent" id="Fact_66f728e151b74fe99d367269b42506b7" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,279</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:LongTermObligationsCurrent" id="Fact_6b303576d07b435ebdc0b94cf229a5a7" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,831</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total Long-Term Obligations</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsNoncurrent" id="Fact_147209ef0e4d4ccf9a6541966995a76b" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,949,502</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsNoncurrent" id="Fact_85488b1118b143d68b8dce7fa49d282e" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,914,112</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c85" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c86">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c86" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c87">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2023, our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c77f6385cafa4ad8bab7f3f3652a99e3" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%
    Notes was classified as a current liability because they matured in December 2024.</div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c87" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c88">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c88" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c89">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt and Call Spread</div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c89" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c810">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c810" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c811">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2be25c7a5c72472e9c15210dd1e5d28a" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction> Percent
    Convertible Senior Notes</div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c811" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c812">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c812" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c813">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2023, we completed a $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_2827f988857f4d83a88b2709d9e03496" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">575.0</ix:nonFraction>
    million offering of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c5215ed19b5d490686fba99e7d7fb4cf" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes and used $<ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_7a3b0ccfb3cb4e9698d4e0b9342decd0" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">488.2</ix:nonFraction>
    million of the net proceeds from the issuance of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2eee1ecf9b9a4c3eb82c9c640e3c9d40" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes to repurchase $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_039a4d1b01a34bf1820a24371b146141" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">504.4</ix:nonFraction> million in principal of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6800a27f69804f25a7df783088a1afb8" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes. In December 2024, we
    used $<ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_42e44c6511874a0ebef7a550dae4a720" contextRef="c20241201to20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">44.5</ix:nonFraction> million of the net proceeds to settle the remaining principal balance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c0a656256d3b41859e2c135ff61aee31" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes upon maturity.</div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c813" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c814">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c814" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c815"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_9db52fd0c4704793bdc5ead80fad4394" contextRef="c20240101to20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" escape="true" continuedAt="Text_4daf6fe3a40247bf8e21ddddfdfa312b1">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2024, we had the
    following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b863244551354c4ba0f150236fa87941" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes outstanding (in millions, except interest rate and price per share data):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c815" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c816"><ix:continuation id="Text_4daf6fe3a40247bf8e21ddddfdfa312b1" continuedAt="Text_4daf6fe3a40247bf8e21ddddfdfa312b2">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c816" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c817"><ix:continuation id="Text_4daf6fe3a40247bf8e21ddddfdfa312b2">
<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_3437b4339a6f44cc995c6a2b53e40971" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_0edf5e00ff7b47ec98064a6ba7db3e26" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">575.0</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredFinanceCostsNet" id="Fact_9bd65cff70f646cc86e02da6375e8233" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.0</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_6bfb094eab7041389566a848570cbbe5">June 2028</span></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e1d091b2df1d47028e7c17396441fb80" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_0dc0b20f31a942798c3ab1359dd806a2" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">2.3</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_f56a3eac5087438ea4564f05d5033780" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">53.73</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_09bd02bea9714ddbb22f039a7b396d9f" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.7</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
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  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c818" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c819">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f5b5a23692f0422d8037c5dd1c16fade" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction> Percent
    Convertible Senior Notes and Call Spread</div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c819" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c820">
<div><br/>
  </div>
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  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c820" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c821">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we completed a $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_e356cca79255453a9744770e7aab33b4" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">632.5</ix:nonFraction>
    million offering of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ae7002548a534fee872a8e938e39b15c" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. We used $<ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_4de3897ac3004dd1afac4be2c42bf1f7" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">319.0</ix:nonFraction>
    million of the net proceeds from the issuance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9978b6fcdd5440e6a17fe410ee220d62" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes to pay the remaining $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_ca75ade69e7442869526532bd706b3dd" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">309.9</ix:nonFraction> million principal balance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9c88b33e6c8542d4a643427942f4e71b" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% convertible senior notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7b4dee93ea894025afe8c897b474b27e" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes, in 2021.</div>
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  </div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-32</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
<div><ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c822" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c823"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_599676c995b8459d807f45a7ee7d2f44" contextRef="c20240101to20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" escape="true" continuedAt="Text_98d967f2a2534393a62e7a21d14e80661">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2024, we had the
    following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_cf6dcedc94a145b888849ad4a5c7cdb5" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes outstanding (in millions, except interest rate and price per share data):</div>
</ix:nonNumeric></ix:continuation>

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<div><br/>
  </div>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6d46b8c9d8784f0fa3a450459c902acb" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_e8faed5233594fb6bf822eaf5dce7321" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">632.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredFinanceCostsNet" id="Fact_350bc75ec4184041835a9e5d0abbe608" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.0</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: top; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_77100aa329424b42b6f03dc4fa1e2472">April 2026</span></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6d45cad18839462fa92cba3b7325e8b0" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_260bb8f54ea846abb3af6de44c421a97" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_4d4305ef91884023b859a267d99ab638" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">57.84</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_0e8e01a4405d49f9b71f725ea3741819" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">76.39</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_9b29e5e197724eaeaa88134c9db47e86" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.9</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c826" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c827">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and
    selling warrants, to minimize the impact of potential economic dilution upon conversion of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b22585535cfb466eb1e1615019206acb" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes by increasing the effective conversion
    price on our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ab040372e7e74fc3812280d6edee6f21" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. We increased our effective conversion price to $<ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_598593809d9544798fe271f12c9023fb" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">76.39</ix:nonFraction> with the same number of underlying shares as our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_cbb00c2783694753bef550b9864ee799" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. The
    call spread cost us $<ix:nonFraction name="ions:CallSpread" id="Fact_129e260b2ff84c1db67e2212a1785983" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">46.9</ix:nonFraction> million, of which $<ix:nonFraction name="us-gaap:PaymentsForHedgeFinancingActivities" id="Fact_25825ced735845a59993eed7890d4b22" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">136.7</ix:nonFraction>
    million was for the note hedge purchase, offset by $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfWarrants" id="Fact_4f7a63f450c14b14afc04dd8bf6effa3" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">89.8</ix:nonFraction> million we received for selling the warrants. Similar to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f0c3c1424f334a3dada4d019d37f7a67" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a887ff3cb730420a8161a0af503a358d" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. The note hedges will expire upon maturity of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_775c5689ca3941d9913a9c6a75bd4518" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%
    Notes, or <span style="-sec-ix-hidden:Fact_c2c8af8268614a7d9201a587fc5822f5">April 2026</span>. The note hedges and warrants are separate transactions and are not part of the terms of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ad5009d3de5c4135aa6fc1d1e09990ca" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. The holders of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c92efdfde6094e73bb58539e70cac496" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes do not
    have any rights with respect to the note hedges and warrants.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a1630fc496cc4b6b8fca442ebcbb1f31" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction> Percent
    Convertible Senior Notes and Call Spread</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of
    our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_741bd24af8454bb8b57e1238ce0f360e" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes to exchange $<ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_8fe4c3bf98884e558d3617a5c9500acd" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">375.6</ix:nonFraction>
    million of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f20ee7aa37e84ac2997fe3950fccd36c" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes for $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_34f127b663394d64a09c8f28308a2191" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">439.3</ix:nonFraction>
    million of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a52eda79373d4bb1be58b66bff61219b" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes, and to issue $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_38bf866f0d0640faa683c6433495028f" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">109.5</ix:nonFraction>
    million of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_06096a47ac82472ba19a888fcbdb199f" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed above, in 2023, we repurchased $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_4ce45938c9ac49109b6af8dd34990118" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">504.4</ix:nonFraction>
    million of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_303242a9804e4932bd78783ac53b820a" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes. As a result of the repurchase, we recognized a $<ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_9b9f41e3cd3b4da69cb768223bcf23ab" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_IncomeStatementLocationAxis_OtherNonoperatingIncomeExpenseMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">13.4</ix:nonFraction> million gain on the early retirement of debt, which we recorded as other income in our consolidated statement of operations for the year ended December 31, 2023. The gain on the early retirement of our debt is the difference between the amounts paid to repurchase our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_26627e77fb794a31a38c5064d6a5a1a6" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes and the net carrying balance of the liability at the time that we completed the repurchases. We paid the remaining principal balance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_01cf54696660421bb8e8fd0d0001599d" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes with $<ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_e1f6dc3a6a3249129c2944be597e37dc" contextRef="c20241201to20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">44.5</ix:nonFraction> million of cash at
    maturity in December 2024.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In conjunction with the issuance of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_3bc795c421da420da2a22d5537147977" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes in 2019, we entered into a call spread transaction, which was
      comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a9e68e18a66c490cbd4de10065e4d2e7" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%
    Notes by increasing the effective conversion price on our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7c1fa536b119496284ec81c1d2ec66af" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We increased our effective conversion price from $</span><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_77047d215260400cbc1d08fbc2b2829a" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">83.28</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to $</span><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_ee1e2d9a0d4f40bda889e2d414ca53ec" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">123.38</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> with the same number of underlying
      shares as our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_547f7d199ac54559bb26fec15121cc0c" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes. The call spread cost us $</span><ix:nonFraction name="ions:CallSpread" id="Fact_e07ddcba2c40439aa143adc7ec803e5c" contextRef="c20190101to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">52.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, of which $</span><ix:nonFraction name="us-gaap:PaymentsForHedgeFinancingActivities" id="Fact_c14c01070e90448bb668496d2df0b9da" contextRef="c20190101to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">108.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million was for the note hedge purchase, offset by $</span><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfWarrants" id="Fact_187977c4a1dc4ec9884c191c74f41f85" contextRef="c20190101to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">56.1</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we received for selling the warrants. Similar to our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_0b2f9f1a5a8a4bac919a9df86ccfd20b" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, our note hedges were subject to adjustment. Additionally, our
      note hedges were exercisable upon conversion of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2f842b01ff1046c3b87d49c91dbe97c9" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The note hedges expired upon maturity of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ae172880ec1c46c0af9cd576a88b5944" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in </span><span style="-sec-ix-hidden:Fact_b2783015cbc64323aab97584a4bd55af">December 2024</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The warrants will expire in
      March 2025. The note hedges and warrants were separate transactions and were not part of the terms of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ea7c588bbe6348e2bc83429f14bfe7d9" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The holders of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e36b3434d50243eebc6487c0d49766c0" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> did not have any rights with respect to the note hedges and warrants.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Other Terms of Convertible Senior Notes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e1b4f4155f854dd78c5c594e31875bca" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_82f1ae3649ac4b75a4132dc445074f98" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash,
    shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of
    certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to <ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_f9d338b32b824c4e9ebf954da5f6382f" contextRef="c20240101to20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_091dcab7068348abb11a9c59de5edaa8" contextRef="c20240101to20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction></ix:nonFraction> percent of the principal
    amount of the notes to be purchased, plus any accrued and unpaid interest. The <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c09d6cb2121b4985876826c4f6fef0cd" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes were subject to similar terms.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our total interest expense for our outstanding senior convertible notes for the years ended December 31, 2024, 2023 and 2022 included $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_05fac467f34b4325a9b3a4217145b9d9" contextRef="c20240101to20241231_DebtInstrumentAxis_ConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.1</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_04b89c3ed7cd436b93a1c06d91163c41" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.9</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_88e0ec7ba1354b8fb9319b06199da578" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.3</ix:nonFraction> million, respectively, of
    non-cash interest expense related to the amortization of debt issuance costs for our convertible notes.</div>
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<div><br/>
  </div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Financing Arrangements</div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Operating Facilities</div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2017, we purchased the building that houses our primary R&amp;D facility for $<ix:nonFraction name="us-gaap:PaymentsToAcquireBuildings" id="Fact_4a0c024b965c4f51b897f9cf5bc80424" contextRef="c20170101to20171231_PropertyPlantAndEquipmentByTypeAxis_PrimaryResearchAndDevelopmentFacilityMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">79.4</ix:nonFraction> million and our manufacturing facility for $<ix:nonFraction name="us-gaap:PaymentsToAcquireBuildings" id="Fact_06974c574f644e5baacbd3f8e2c599a6" contextRef="c20170101to20171231_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">14.0</ix:nonFraction> million. We
    financed the purchase of these <ix:nonFraction name="ions:NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" id="Fact_802514d6121f4f3ca8efa9133eb869cd" contextRef="c20170101to20171231" unitRef="U016" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> facilities with mortgage debt of $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_1c1b0d341f0d4a39b8dd7164eab2e39d" contextRef="c20171231_DebtInstrumentAxis_LongTermMortgageDebtMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">60.4</ix:nonFraction> million in total. Our primary R&amp;D facility mortgage had an interest rate of <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2e21e0a6347e447a8991607c0227050a" contextRef="c20171231_PropertyPlantAndEquipmentByTypeAxis_PrimaryResearchAndDevelopmentFacilityMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">3.88</ix:nonFraction>
    percent. Our manufacturing facility mortgage has an interest rate of <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b8df62c274f14f0499a84c79aa3dd4f9" contextRef="c20171231_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">4.20</ix:nonFraction> percent. During the first <ix:nonNumeric name="ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" id="Fact_cec9dfdd051e4462bf766547d85be9b4" contextRef="c20240101to20241231_DebtInstrumentAxis_ManufacturingFacilityMortgageMember" format="ixt-sec:durwordsen"><ix:nonNumeric name="ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" id="Fact_885a5330a5d64c1ca25849873c2df457" contextRef="c20240101to20241231_DebtInstrumentAxis_PrimaryResearchAndDevelopmentFacilityMortgageMember" format="ixt-sec:durwordsen">five years</ix:nonNumeric></ix:nonNumeric> of both mortgages, we were only required to make interest payments. We began making principal payments in 2022. Our manufacturing facility mortgage matures in August
    2027. We repaid our primary R&amp;D facility mortgage in 2022 in conjunction with a sale and leaseback transaction.</div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, we concurrently entered into <ix:nonFraction name="ions:NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" id="Fact_8733f15524b344938a5622966d91cd3f" contextRef="c20220101to20221231" unitRef="U017" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction>
    purchase and sale agreements with a real estate investor. In the same period, we closed the first transaction in which we sold the facilities at our headquarters in Carlsbad, California, which includes our primary R&amp;D facility, for a purchase price
    of $<ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_995ff98913014ef6a5f5fc51445c7128" contextRef="c20220101to20221231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">263.4</ix:nonFraction> million. As a result, we de-recognized the related land and improvements, building and building improvements, which resulted in a net
    gain of $<ix:nonFraction name="us-gaap:GainLossOnDispositionOfAssets1" id="Fact_e1b424eff905493698bc9b6f4316f08f" contextRef="c20220101to20221231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">150.1</ix:nonFraction> million that we reported in other income in our consolidated statements of operations. We used a portion of the sale proceeds to
    extinguish our outstanding mortgage debt on our primary R&amp;D facility of $<ix:nonFraction name="us-gaap:RepaymentsOfSecuredDebt" id="Fact_ee22c79230e54d5289dec6e7979e0722" contextRef="c20220101to20221231_DebtInstrumentAxis_PrimaryResearchAndDevelopmentFacilityMortgageMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">51.3</ix:nonFraction> million. In connection with this transaction, we leased back
    our headquarters facilities for an initial lease term of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_e6d37e165f84425ea9db0bd0fa02c2cf" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" format="ixt-sec:duryear">15</ix:nonNumeric> years with options to extend the lease for <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_0746b48df37641eaab4f8443ed332073" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> additional terms of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_693e91d48d5b4feebec724ed9ff884f7" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" format="ixt-sec:durwordsen">five years</ix:nonNumeric> each.</div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2023, we closed the second transaction and transferred legal ownership of <ix:nonFraction name="ions:NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" id="Fact_a8c5588ea2e04cc99ff52c8cb117bb7b" contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_LandMember" unitRef="U018" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> lots of undeveloped land adjacent to our headquarters to the real estate investor for a purchase price of $<ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_c3af5a38042e409fa61183221c638107" contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_LandMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">33</ix:nonFraction> million. In connection with this transaction, we entered into a build-to-suit lease agreement with the same real estate investor to lease a new R&amp;D facility. The lessor will
    develop and construct a new building composed of R&amp;D and office space. We will design and construct tenant improvements to customize the facility&#8217;s interior space. We will lease the facility for an initial term of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_e198dab14cc74d2fadbd634160d04423" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" format="ixt-sec:duryear">15</ix:nonNumeric> years with options to extend the lease for <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_23a41853ffc14bdb96e6c3de4058ab3a" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction>
    additional terms of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_782a866aae5e44f4a70dc6a5aa6bd1b5" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" format="ixt-sec:durwordsen">five years</ix:nonNumeric> each. The lease will commence once the structure of this new facility is completed.</div>
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<div><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Since the building is under construction and unavailable to lease, we are unable to complete the sale-leaseback evaluation under ASC 842,
    <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</span>. As a result, the land remains in our consolidated balance sheets and we accounted for the proceeds as a financial liability. We will
    reassess the transaction under the sale-leaseback accounting guidance when the facilities are available for lease commencement.</div>
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<div><br/>
  </div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Debt Maturity Schedules</div>
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<div><br/>
  </div>
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  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c860" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c861"><ix:nonNumeric name="srt:ContractualObligationFiscalYearMaturityScheduleTableTextBlock" id="Text_16539426e6924191b5cc465550dba8af" contextRef="c20240101to20241231" escape="true" continuedAt="Text_948605b9a92b467498a2deb758e852a01">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2024 are as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c861" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c862"><ix:continuation id="Text_948605b9a92b467498a2deb758e852a01" continuedAt="Text_948605b9a92b467498a2deb758e852a02">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c862" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c863"><ix:continuation id="Text_948605b9a92b467498a2deb758e852a02">
<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2025</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" id="Fact_d2eb54062a6d4f188ef1dbae3b8653d3" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,657</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2026</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" id="Fact_c42e928b65cd45aa923675e567769ac7" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">643,157</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2027</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" id="Fact_6b7eb3455bef4825bec5934f0ca8a9f2" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2028</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" id="Fact_5163088d8dfb4bd8afb6a945c3e15b83" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">580,091</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2029</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" id="Fact_04194527fb664e52a3ac79595e34b654" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">60</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive" id="Fact_74f3f2a83bb64af5b0b4b21df7d35ef0" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">360</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt and mortgage maturities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebt" id="Fact_41f58f8c96774a38af7b7c1cc41eabb9" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,253,062</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion included in other current liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:LongTermDebtCurrent" id="Fact_bc879ac3c37f49de90a976632193e86e" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">165</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Fixed and determinable interest</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestPayableCurrentAndNoncurrent" id="Fact_ef9db53e88e14db9b13d2afa08b9cc23" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">36,511</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Debt issuance costs</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredFinanceCostsNet" id="Fact_97e59891cc4a4a90baf9d56b32982707" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">13,981</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtNoncurrent" id="Fact_2e8033307b594b4f9b2e30ee6ba95bc3" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,202,405</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
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<div><ix:nonNumeric name="us-gaap:LesseeOperatingLeasesTextBlock" id="Text_816a383efe384026825a397c06709b4a" contextRef="c20240101to20241231" escape="true" continuedAt="Text_c72f602f5d7841a0b05d292b6f2a2a541">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Operating Leases</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Carlsbad Leases</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing
    facility. We lease this space under a non-cancelable operating lease. In 2020, we exercised our option to extend our lease, extending our lease term from June 2021 to August 2026. We have <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_f720c6530d1d4a0a9db7c9c5651ae759" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadFacilityMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> remaining option to extend the lease for an additional <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_c08e7408596346fea9c2156de05912d7" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadFacilityMember" format="ixt-sec:durwordsen">five-year</ix:nonNumeric>
    period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also lease an additional office space and warehouse space in Carlsbad. We lease these spaces under non-cancelable operating leases. In
    2022, we exercised our option to extend the office space lease, extending our term from January 2023 to May 2027. We have <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_fda06318ab41423f9e871d23c3ba6480" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadOfficeSpaceMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> remaining options
    to extend this lease. Our warehouse space lease in Carlsbad has an initial term ending in 2028 with <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_08797d9de1754a398e2476e465a5a05d" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadWarehouseSpaceMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> options to extend the lease.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed above in the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Financing Arrangements</span>, we lease our headquarters, which includes our primary R&amp;D facility, as part of a sale and leaseback transaction that closed in 2022. The initial lease term for our headquarters facilities is <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_7f2058c8172e474bbf205fda14546132" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" format="ixt-sec:duryear">15</ix:nonNumeric> years with options to extend the lease for <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_2ee2e32f70634bcfa6b92ccee44f0bdf" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction>
    additional terms of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_1488c1954cd849a1a4f6161cf2b82691" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" format="ixt-sec:durwordsen">five years</ix:nonNumeric> each. We determined at lease inception that it was not reasonably certain that we would exercise any of the
    options to extend the lease. We expect our lease payments over the initial term to total approximately $<ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue" id="Fact_a1b244754eec475a945bcce4913ec530" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">280</ix:nonFraction> million. In connection with the
    transfer of legal ownership of the <ix:nonFraction name="ions:NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" id="Fact_17aadca36cd14bb7b824374f744e4abc" contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U018" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> lots of undeveloped land to the real estate investor, we entered into a build-to-suit lease agreement
    with the same real estate investor who will build a new R&amp;D facility for us on those lots. The lease will commence once the structure of this new facility is completed.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Oceanside Lease</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility to be constructed by
    the lessor in Oceanside, California. We capitalized costs that we incurred related to the design and development of tenant improvements as construction-in-progress in our consolidated balance sheets. In 2023, we reached a mutual agreement with the
    lessor to terminate the lease agreement. As a result, we recorded a charge of $<ix:nonFraction name="us-gaap:ImpairmentOfLongLivedAssetsHeldForUse" id="Fact_171f16cc89494c4ea4ec3ca4d9a325d8" contextRef="c20230101to20231231_PropertyPlantAndEquipmentByTypeAxis_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction> million, primarily associated with the impairment of
    construction-in-progress assets, within <span style="-sec-ix-hidden:Fact_ebdf1ed5cf6845079198439e7c520f42">SG&amp;A expense</span> in our consolidated statements of operations.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Boston Leases</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We entered into an operating lease agreement for office space located in Boston, Massachusetts which commenced in August 2018. We are
    leasing this space under a non-cancelable operating lease with an initial term ending after <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_1cf767bfa2604645b03665b44c8069bb" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember" format="ixt-sec:durmonth">123</ix:nonNumeric> months and an option to extend the lease for an
    additional <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_c9d11c93abf3409aab88ca3e2efcb6a1" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember" format="ixt-sec:durwordsen">five-year</ix:nonNumeric> term. Under the lease agreement, we received a <ix:nonNumeric name="ions:LesseeOperatingLeasePeriodOfFreeRent" id="Fact_ba6fa8c8bcc140258a36c6828c2ab217" contextRef="c20240101to20241231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember" format="ixt-sec:durwordsen">three-month</ix:nonNumeric> free rent period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commencement date was in
    January 2022 when the office space was ready for our tenant&#8217;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending <ix:nonNumeric name="us-gaap:LessorOperatingLeaseTermOfContract" id="Fact_f3673b6f6d8a469cb3fc9b19fe6c9445" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember" format="ixt-sec:durmonth">83</ix:nonNumeric> months following the sublease commencement date with <ix:nonFraction name="ions:LessorOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_8c1775b36c92469e9d8ba3d06078efc9" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> option to extend the sublease. Under the sublease
    agreement we provided a <ix:nonNumeric name="ions:LessorOperatingLeasePeriodOfFreeRent" id="Fact_bdb3d42dbeaf484494c12e827a769a24" contextRef="c20240101to20241231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember" format="ixt-sec:durwordsen">seven-month</ix:nonNumeric> free rent period, which commenced in January 2022. We will receive lease payments over the sublease term
    totaling $<ix:nonFraction name="us-gaap:LessorOperatingLeasePaymentsToBeReceived" id="Fact_7c8de04d910848adb798d3e411c0825d" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">9.6</ix:nonFraction> million.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We entered into an operating lease agreement for another office space located in Boston, Massachusetts which commenced in 2021. We are
    leasing this space under a non-cancelable operating lease with an initial term ending <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_f252e6bc1ca849dfb22869bd4a71369a" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember" format="ixt-sec:durmonth">91</ix:nonNumeric> months following the lease commencement date and an
    option to extend the lease for <span style="-sec-ix-hidden:Fact_ddceec580074417fbe536c7c2d5d252c">an</span> additional <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_093b7e88a1474547a8fe7129936aa7cd" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember" format="ixt-sec:durwordsen">five-year</ix:nonNumeric>
    term. Under the lease agreement, we received a <ix:nonNumeric name="ions:LesseeOperatingLeasePeriodOfFreeRent" id="Fact_99931a7181e04c71bbd9180a5f64f952" contextRef="c20240101to20241231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember" format="ixt-sec:durwordsen">seven-month</ix:nonNumeric> free rent period, which commenced in November 2021. Our lease payments over the
    initial term total $<ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue" id="Fact_c350c485d2194852998ea1b496903ff5" contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.8</ix:nonFraction> million.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases, we did not include
    the extension options for these leases in the original lease term because it was not reasonably certain we would exercise those extension options.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
  </div>
</ix:continuation></ix:continuation>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At December 31, 2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use operating lease assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAsset" id="Fact_42b72db309654cf1bdbfe546a3a2176d" contextRef="c20241231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">161.9</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating lease liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseLiability" id="Fact_44caa1523d334df48c7b2561738097e4" contextRef="c20241231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">170.9</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average remaining lease term</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1" id="Fact_ccfd1bbd8568445fb43b6a1d85973cc7" contextRef="c20241231" format="ixt-sec:duryear">12.1</ix:nonNumeric> years</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average discount rate</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent" id="Fact_0f6726aa9c174130a3010b4dad4799ef" contextRef="c20241231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">6.9</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
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  </div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-35</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024,
    2023, and 2022 we paid $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_826cead5743b4e90a9d8b807e97fe422" contextRef="c20240101to20241231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">20.5</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_297fcce7f2e44b348fe63e7be360cf7c" contextRef="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">20.1</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_50e928616e964a8c94f28d1e4409995c" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.0</ix:nonFraction> million of lease payments, which were included in operating activities in our consolidated statements of cash flows.</div>
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  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024,
    the future payments for our operating lease liabilities are as follows (in thousands):</div>
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<div><br/>
  </div>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</span> <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</span></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Year ending December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" id="Fact_9240bc8118ea402f85a2119c7486d19d" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,870</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2026</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" id="Fact_4609f99ef9604c9aae3baed51a3c3fed" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">21,032</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2027</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearThree" id="Fact_d11239309f5945a3891ef526d1491daa" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">21,054</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2028</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFour" id="Fact_43a6c7550e004272b7f9ca99a8ba22d8" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,973</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2029</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFive" id="Fact_74899d789ebf4c2ebccd545b74c63e21" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,687</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" id="Fact_3931369a624044a9b1905cb93b92544f" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">157,622</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total minimum lease payments</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue" id="Fact_3603a725690b46dda9be3db4e21043c4" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">260,238</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: left; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Imputed interest</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" id="Fact_6d8e7a3e7ccb4ac9a37ea341d9cadf8c" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">89,369</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion (included in <span style="-sec-ix-hidden:Fact_9874929ec96442469df0f0fc39baed32">other current liabilities</span>)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingLeaseLiabilityCurrent" id="Fact_599739bca7c14726b6810c3c3a59fcff" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,064</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px;">
          <div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term lease liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseLiabilityNoncurrent" id="Fact_5bc4a22d2bca49aca884201dc1170194" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">161,805</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_c72f602f5d7841a0b05d292b6f2a2a5433" continuedAt="Text_c72f602f5d7841a0b05d292b6f2a2a5434">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_c72f602f5d7841a0b05d292b6f2a2a5434">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Rent expense was $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_b625c294a3bd434f8c74620b51e1ea20" contextRef="c20240101to20241231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.2</ix:nonFraction> million,
    $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_37e7125f4da2437a81d1b7f1853e4554" contextRef="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.1</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_a6f37ce5e1654e67b6bfb04f2bfaa94b" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.3</ix:nonFraction> million for the
    years ended December 31, 2024, 2023
    and 2022, respectively. </div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c863" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c864">
<div><br/>
  </div>
</ix:continuation></div>

  <div>
    <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c864" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c865">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Royalty Revenue Monetization</div>
</ix:continuation>
  </div>

  <div>
    <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c865" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c866">
<div><br/>
    </div>
</ix:continuation>
  </div>
<div><ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c866" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c867">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our agreements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $<ix:nonFraction name="ions:UpfrontRoyaltyPaymentReceived" id="Fact_c8ba625af5db4c629715e10efedcdff1" contextRef="c20230101to20230131" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">500</ix:nonFraction> million and we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForAdditionalMilestones" id="Fact_d5508d985dec4c9299c67fd453890fd5" contextRef="c20230131" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">625</ix:nonFraction> million in additional milestone payments. Under the terms of
    the agreement, Royalty Pharma will receive <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_04d45df1075f4c7282dba5c75f87090a" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_7db57813067c495a9024650b8968a999" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">45</ix:nonFraction> percent of royalty payments in 2028, on up to $<ix:nonFraction name="ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" id="Fact_9f09740d482b4450bde402e99f9264a9" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.5</ix:nonFraction>
    billion in annual sales. In addition, Royalty Pharma will receive <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_4f14fcd874cc407499d3f48e153e6244" contextRef="c20230131_ProductOrServiceAxis_PelacarsenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of any future royalty payments on pelacarsen. Royalty Pharma&#8217;s
    royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $<ix:nonFraction name="ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" id="Fact_2203af9e770d4ee987086d61868bd2ee" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">475</ix:nonFraction> million or $<ix:nonFraction name="ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" id="Fact_dcfdc1338630420c9019168b9412101d" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">550</ix:nonFraction> million, depending on the timing and occurrence of FDA approval of pelacarsen.</div>
</ix:continuation>

  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c867" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c868">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c868" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c869">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the upfront payment of $<ix:nonFraction name="ions:UpfrontRoyaltyPaymentReceived" id="Fact_f0e73629c96a44169a5a0e9d8a1d4b9a" contextRef="c20230101to20230131" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">500</ix:nonFraction>
    million as a liability related to the sale of future royalties, net of transaction costs of $<ix:nonFraction name="ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_1391ba32fa9a456194c1aa68413d1b61" contextRef="c20240101to20241231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.4</ix:nonFraction> million, which we are amortizing over the
    estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty
    Pharma as a reduction of the liability.</div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c869" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c870">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c870" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c871">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We determine the effective interest rate used to record
      interest expense under this agreement based on an estimate of future royalty payments to Royalty Pharma. As of </span>December 31, 2024 and
    2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the estimated effective interest rate under the agreement
      was </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_ec437319099f426c8aa516986b8454b2" contextRef="c20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_d7d548cc748640208f68b9bf1f4a17e2" contextRef="c20241231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">13.5</ix:nonFraction></ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c871" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c872">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c872" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c873"><ix:nonNumeric name="us-gaap:OtherNoncurrentLiabilitiesTableTextBlock" id="Text_21736a72e1aa4319a1ee1097952860ac" contextRef="c20240101to20241231" escape="true" continuedAt="Text_d158689ff8614e69a2eb56706aa0dbaf1">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our liability related to
      sale of future royalties for the year ended </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands):</span></div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c873" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c874"><ix:continuation id="Text_d158689ff8614e69a2eb56706aa0dbaf1" continuedAt="Text_d158689ff8614e69a2eb56706aa0dbaf2">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_91ca864fbc6e416294ee9c4af8a359c874" continuedAt="Text_91ca864fbc6e416294ee9c4af8a359c875"><ix:continuation id="Text_d158689ff8614e69a2eb56706aa0dbaf2">
<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of future royalties in January 2023</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ProceedsFromSaleOfFutureRoyalties" id="Fact_b900ad354383483f9c34ba3b6c879d07" contextRef="c20230101to20230131_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">500,000</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance costs related to sale of future royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_06f0683a1ee2471e904766301687d1bf" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,434</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty payments to Royalty Pharma</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:RoyaltyPayments" id="Fact_67ccd0c0a7a24a5f910faba6121087a7" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">44,628</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:InterestExpenseRelatedToSaleOfFutureRoyalties" id="Fact_a9cc1712c3f242eb9a739d51e13366c1" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">68,238</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_3d02b819626e4086983fa9341d4831c8" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">560</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of December 31, 2023</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet" id="Fact_4131f58396f64f56b46e5c98c24b4b09" contextRef="c20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">513,736</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty payments to Royalty Pharma</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:RoyaltyPayments" id="Fact_a85f9bc10ae941708721d1677033a9ce" contextRef="c20240101to20241231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">44,981</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:InterestExpenseRelatedToSaleOfFutureRoyalties" id="Fact_99d39bc987474b1a9b5a52fa2ff937d9" contextRef="c20240101to20241231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">72,846</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_0c2530763c2d4d60b6b285619ac51eed" contextRef="c20240101to20241231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">611</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; padding-bottom: 4px;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of December 31, 2024</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet" id="Fact_5aabe7b33b4a451bb364f48681f15dbe" contextRef="c20241231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">542,212</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;">&#160;</td>

  </tr>


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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty
    payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the commercial sales of SPINRAZA, the regulatory approval and commercial sales of
    pelacarsen, competing products or other significant events.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">8. Stockholders</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> Equity</span></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Preferred Stock</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are authorized to issue up to <ix:nonFraction name="us-gaap:PreferredStockSharesAuthorized" id="Fact_cdf2c784100f453c85b910f7ffa74a1e" contextRef="c20241231_StatementClassOfStockAxis_PreferredStockMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction>
    million shares of &#8220;blank check&#8221; Preferred Stock. As of December 31, 2024, there were <ix:nonFraction name="us-gaap:PreferredStockSharesOutstanding" id="Fact_9e3c83d35b1a4ad9bb5804db20a70950" contextRef="c20241231_StatementClassOfStockAxis_PreferredStockMember" unitRef="U002" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> shares of Preferred Stock outstanding. We have designated Series C Junior Participating Preferred Stock but have <ix:nonFraction name="us-gaap:PreferredStockSharesOutstanding" id="Fact_56071bcb2d56480397a630e97def5c32" contextRef="c20241231_StatementClassOfStockAxis_SeriesCPreferredStockMember" unitRef="U002" decimals="INF" scale="0" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:PreferredStockSharesIssued" id="Fact_5fe1b66991274e8cbc8b7286eae05354" contextRef="c20241231_StatementClassOfStockAxis_SeriesCPreferredStockMember" unitRef="U002" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction> issued or outstanding shares as of December 31, 2024.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Common Stock</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2024 and 2023, we had <ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_292edcba897f40209ed42c14feed0f2e" contextRef="c20231231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_10c668f50b664401a30c1bb6a51edb5a" contextRef="c20241231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">300</ix:nonFraction></ix:nonFraction> million shares of common
    stock authorized, of which <ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_6d69412111c94f649e3bc6185a645456" contextRef="c20241231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_5f23b4a620974ffa9ac1338867c08a09" contextRef="c20241231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">157.9</ix:nonFraction></ix:nonFraction> million and <ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_eba69077d17e4204b64b00ee384f8ab0" contextRef="c20231231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_7461dbbf5e58485bbd613618075e0ee5" contextRef="c20231231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">144.3</ix:nonFraction></ix:nonFraction> million were issued and outstanding, respectively. As of December 31, 2024, total common shares
    reserved for future issuance were <ix:nonFraction name="us-gaap:CommonStockCapitalSharesReservedForFutureIssuance" id="Fact_47e88bfdb1664c48a2b1ff64f80389f5" contextRef="c20241231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">48.0</ix:nonFraction> million.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024,
    2023 and 2022, we issued <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_0ee4b00a77834001bc604428d95159c5" contextRef="c20240101to20241231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.1</ix:nonFraction> million, <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_6d8eb059ce834187b603ca07d5abb207" contextRef="c20230101to20231231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.3</ix:nonFraction> million and <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_edd10ce23a74492e8176afb94a7abdb0" contextRef="c20220101to20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.2</ix:nonFraction> million shares of common stock, respectively, for stock option exercises, vesting of restricted stock units, and ESPP purchases. We received net
    proceeds from these transactions of $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_d6943984a2cd41b0a8cb3b1deb1f9fc2" contextRef="c20240101to20241231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">33.6</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_5fbad294b6304ae4a8a72a7d07384a09" contextRef="c20230101to20231231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">49.4</ix:nonFraction>
    million and $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_4af5fbc849034e59b7d2901adc45af29" contextRef="c20220101to20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.4</ix:nonFraction> million in 2024, 2023 and 2022, respectively.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2024, we completed the sale of <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesNewIssues" id="Fact_d610ade5082c4fd3ae1f895c9fe9db15" contextRef="c20240901to20240930_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">11.5</ix:nonFraction>
    million shares of our common stock through a public offering at a price of $<ix:nonFraction name="us-gaap:SharesIssuedPricePerShare" id="Fact_0e7d05d0f5384003b14dbb190182b1f9" contextRef="c20240930_StatementClassOfStockAxis_CommonStockMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">43.50</ix:nonFraction> per share. We received net proceeds of $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfCommonStock" id="Fact_30a78063f7104495b4d4f36c85798dd3" contextRef="c20240901to20240930_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">489.1</ix:nonFraction> million from the sale of these shares net of underwriting discounts and commissions and other offering expenses of $<ix:nonFraction name="us-gaap:PaymentsOfStockIssuanceCosts" id="Fact_54bbb168cc0b43b8b1de4c2e0dff981c" contextRef="c20240901to20240930_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">11.2</ix:nonFraction> million.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock Plans</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1989 Stock Option Plan</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 1989, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that, as amended, provides for
    the issuance of non-qualified and incentive stock options for the purchase of up to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_2a82263b39a7474ba2b3298ff2f3a349" contextRef="c20241231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">20.0</ix:nonFraction> million shares of common stock to our employees,
    directors, and consultants. The plan expired in January 2024. The 1989 Stock Option Plan, or 1989 Plan, did not allow us to grant stock bonuses or restricted stock awards and prohibited us from repricing any options outstanding under the plan unless
    our stockholders approved the repricing. Options vested over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_300b6e73bf984f4ba7b411e09fd8ac0a" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period, with <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_37deea793758485bbcc993618a0f25e2" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent exercisable at the end of <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" id="Fact_8c42e3e31eb04afc9a1a6d089d774313" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric> from the date of the grant
    and the balance vested ratably, on a monthly basis, thereafter and had a term of <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_7077ae6833184dee85f5278742d25b56" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric>. At December 31, 2024, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_aac422de44984b5691b8963611354e87" contextRef="c20241231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-3" scale="3" format="ixt-sec:numwordsen">no</ix:nonFraction> options were outstanding and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_8c931ba74e0d4e5c8d57ed4b294c4a22" contextRef="c20241231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-3" scale="3" format="ixt-sec:numwordsen">no</ix:nonFraction> shares were available for future grant under the 1989 Plan.</div>
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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2011 Equity Incentive Plan</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the issuance of
    stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to our employees, directors, and consultants. In June 2015, May 2017 and June 2019, after receiving approval from our
    stockholders, we amended our 2011 Equity Incentive Plan, or<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 2011 Plan,</span> to increase the total number of shares reserved for issuance. We increased the shares available
    under our 2011 Equity Incentive Plan from <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_5882aa832aa646c6b635e3bfe41d5f81" contextRef="c20150531_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.5</ix:nonFraction> million to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_1f00ba80dcbf4591a6c03449d0ff3e6e" contextRef="c20150630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">11.0</ix:nonFraction> million in June 2015, from <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_b4182e47d22e4ab1b6c25c3beae739b7" contextRef="c20150630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">11.0</ix:nonFraction> million to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_73b32b7412144ae2844353056c2328ce" contextRef="c20170531_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">16.0</ix:nonFraction> million in May 2017 and from <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_67f1d774e8d34fbbbdcb82cbb830d91a" contextRef="c20170531_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">16.0</ix:nonFraction> million to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_dd1127c8a7ec4eedb63afb7ca6169e93" contextRef="c20190630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.0</ix:nonFraction> million in June 2019. In June 2021, after receiving approval from our stockholders, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2011 Plan. The amendment increased the total number of shares of common stock authorized for issuance under the 2011 Plan from </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_57cfec8e7dd44452863fefb2e13edfc5" contextRef="c20190630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.0</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_de84fcdda0694d5aa3e5b25edbac3ff6" contextRef="c20210630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">29.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and added a fungible share counting ratio whereby the share reserve will be reduced by </span><ix:nonFraction name="ions:IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" id="Fact_23f42a38660942f6be12a03f919b693c" contextRef="c20210630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="1" sign="-" scale="0" format="ixt:num-dot-decimal">1.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> shares for each share of common stock issued pursuant to a full value award (i.e., RSU or PRSU) and
      increased by </span><ix:nonFraction name="ions:IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward" id="Fact_4de4ba08df4c4468acb8a87fe4bb1be6" contextRef="c20210630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="1" scale="0" format="ixt:num-dot-decimal">1.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> shares for each share of common stock
      returning from a full value award. </span>In June 2023, after receiving approval from our stockholders, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2011 Plan to increase the total number of shares of
      common stock authorized for issuance under the 2011 Plan from </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_441bcd9f19644c13947731bccdf147fa" contextRef="c20210630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">29.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_fdc58c93dda24d23a21b330e207c7f2c" contextRef="c20230630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">35.2</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. </span>In June 2024,
    after receiving approval from our stockholders, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2011 Plan to increase the total number of shares of common stock authorized for issuance under the 2011 Plan
      from </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_5e98f0c8a84b4308a968d79a3935981e" contextRef="c20230630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">35.2</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_21739bf69c1246b28db4ef07d7508676" contextRef="c20240630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">38.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The plan expires in June 2031. The 2011 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock
    appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our
    stockholders approve such action. Currently we anticipate awarding only stock options, RSU and PRSU awards to our employees, directors and consultants. Options vest over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_763f3de6711b427ba6c4d7792811777d" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period, with <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_13d5cd5cb0eb4f0e964e186051bcf7a9" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent exercisable at the end of <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" id="Fact_3a3d9b453a064adea83801f87842c09c" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric> from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_7cc41a014493404ba087ca86ab407ebe" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric>. Options granted after December 31, 2021 have a term of <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_c3a19253882c43ce8572c4be5c36bb38" contextRef="c20240101to20241231_AwardDateAxis_IssuedAfterDecember312021Member_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">ten years</ix:nonNumeric>.
    We have granted restricted stock unit awards to our employees under the 2011 Plan which vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_323dc3ca223441ed8cae26677d80920d" contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. At December 31, 2024, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_f6eb4ef69d9549b79f43b5ca7f3d3f65" contextRef="c20241231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">13.3</ix:nonFraction> million
    options were outstanding, of which <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_c37dd0f781d649a5bc97d2c87bbaeacf" contextRef="c20241231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">9.0</ix:nonFraction> million were exercisable, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber" id="Fact_f19dff70c85e4b53ab5b44f7e4b872f2" contextRef="c20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.9</ix:nonFraction> million restricted stock unit awards were outstanding, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_f121d278af9942b4ba6d23912dbef6db" contextRef="c20241231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.3</ix:nonFraction> million shares were available for future grant
    under the 2011 Plan.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the 2011 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur. In addition, we implemented a change of control and severance benefit plan that provides for change of control and severance benefits to our executive officers, including our
    chief executive officer and chief financial officer, and vice presidents. If <ix:nonFraction name="ions:NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" id="Fact_8f959a059fb340fc9f6dfdc4cbdfc6d9" contextRef="c20240101to20241231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U020" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> of our executive officers or vice presidents is terminated or
    resigns for good reason during the period that begins <ix:nonNumeric name="ions:PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" id="Fact_5cf8f8a57af249d4a6cce115597f8861" contextRef="c20240101to20241231_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">three months</ix:nonNumeric> before and ends <ix:nonNumeric name="ions:PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" id="Fact_4b4db5c64d7f42eca6f341535cd62db4" contextRef="c20240101to20241231_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">twelve months</ix:nonNumeric> following a change in control of the company, the impacted employee&#8217;s stock options and RSUs vesting will accelerate for options and RSUs outstanding as of the
    termination date.</div>
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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2020 Equity Incentive Plan</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In connection with the Akcea Merger in 2020, we assumed the
      unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or
      2020 Plan. The 2020 Plan provided for the issuance of up to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_c2fdd0b5f17c4a559deafa59528e79eb" contextRef="c20201231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million shares of our Common Stock to our employees, directors and consultants who were employees of Akcea prior to the Akcea Merger. In the second quarter of 2021, our Compensation Committee approved an amendment to the 2020 Plan. The
      amendment decreased the total number of shares of common stock authorized for issuance under the 2020 Plan from approximately </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_b0e9739857ca4a9ca5aef49a60ac50e3" contextRef="c20201231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_c1bebf52134d402a8958171cfbc5c265" contextRef="c20210630_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. We assumed the 2020 Plan in connection with Ionis&#8217; reacquisition of all of the outstanding shares of Akcea Therapeutics, Inc. as part of the Akcea Merger.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The plan expires in December 2025. The 2020 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock
    appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our
    stockholders approve such action. Currently we anticipate awarding only stock options and RSU awards to our eligible employees, directors and consultants. Options vest over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_f1c93af494b04abea846be47da9b6f21" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period, with <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_bf4c2072cc4b4282835c60cb240d0d17" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent exercisable at the end of <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" id="Fact_6ad6746c60684d1cade6e5856104044e" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric> from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_83e080be39814e6ba0c957ebe364dd77" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric>. Options granted after December 31, 2021 have a term of <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_8c17823f65d24056a081b6cf50f1e55f" contextRef="c20240101to20241231_AwardDateAxis_IssuedAfterDecember312021Member_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen">ten years</ix:nonNumeric>.
    We have granted restricted stock unit awards to our employees under the 2020 Plan which vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_3568607a84604758a037e6132fdacf7c" contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. At December 31, 2024, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_7b23f3391b8648699d7f9d9bdfc98ad2" contextRef="c20241231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.5</ix:nonFraction> million
    options were outstanding, of which <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_6b4dbdd5c0164b6fb94f3a918f49204a" contextRef="c20241231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.2</ix:nonFraction> million were exercisable, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber" id="Fact_998c6813ad25478d8df2ef4e673ad903" contextRef="c20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.2</ix:nonFraction> million restricted stock unit awards were outstanding, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_445e0eb67023409bac8ed8d6e705c2d6" contextRef="c20241231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.8</ix:nonFraction> million shares were available for future grant
    under the 2020 Plan.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the 2020 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the event of certain significant corporate transactions, our Board of Directors has the discretion to take one or more of the following
    actions with respect to outstanding stock awards under the 2011 and 2020 Plans:</div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for assumption, continuation, or substitution of a stock award by a surviving or acquiring entity (or its parent company);</div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the assignment of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award to the surviving or
            acquiring corporation (or its parent company);</div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">accelerate the vesting and exercisability of a stock award followed by the termination of the stock award;</div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the lapse of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award;</div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cancel or arrange for the cancellation of a stock award, to the extent not vested or not exercised prior to the effective date of the corporate transaction, in exchange
            for cash consideration, if any, as the Board, in its sole discretion, may consider appropriate; and</div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the surrender of a stock award in exchange for a payment equal to the excess of (a) the value of the property the holder of the stock award would have
            received upon the exercise of the stock award, over (b) any exercise price payable by such holder in connection with such exercise.</div>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-38</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2002 Non-Employee Directors&#8217; Stock Option Plan</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2001, our Board of Directors adopted, and the stockholders subsequently approved, an amendment and restatement of the 1992 Non-Employee
    Directors&#8217; Stock Option Plan, which provides for the issuance of non-qualified stock options and restricted stock units to our non-employee directors. The name of the resulting plan is the 2002 Non-Employee Directors&#8217; Stock Option Plan, or the 2002
    Plan. In 2015, after receiving approval from our stockholders, we amended our 2002 Plan to increase the total number of shares reserved for issuance from <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_0e9dea3a9bb44f258d4a6a1eeffbb1b0" contextRef="c20141231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.2</ix:nonFraction>
    million to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_e55c20e37dc6464eb74bde99a3d220dc" contextRef="c20151231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.0</ix:nonFraction> million. In 2020, after receiving approval from our stockholders, we further amended our 2002 Plan. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The amendments included:</span></div>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">An increase to the total number of shares reserved for issuance under the plan from </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_fda3670487384cb49c8eb41d6d8f4665" contextRef="c20151231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.0</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_8b16c9fcbd8a4de6a3ff40e97438a3a8" contextRef="c20201231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.8</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million shares;</span></div>
        </td>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A reduction to the amount of the automatic awards under the plan;</div>
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</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A revision to the vesting schedule of new awards granted; and</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An extension of the term of the plan.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Options under this plan expire <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_e6b00753880241348e596a82fa22bab2" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" format="ixt-sec:durwordsen">10 years</ix:nonNumeric>
    from the date of grant. At December 31, 2024, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_28beff5bd3d14e0c9936c3a0e4bfd184" contextRef="c20241231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.9</ix:nonFraction> million options were outstanding, of which <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_5c3c554e640546a481c2968b37014870" contextRef="c20241231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.8</ix:nonFraction> million were exercisable, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber" id="Fact_52cd031e53a5493d8ae9f30994d9f850" contextRef="c20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">52</ix:nonFraction>,000 restricted stock unit awards were outstanding, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_03da27efb55141628520731fb9e70ab8" contextRef="c20241231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.4</ix:nonFraction> million
    shares were available for future grant under the 2002 Plan.</div>
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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Purchase Plan</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2009, our Board of Directors adopted, and the stockholders subsequently approved, the amendment and restatement of the ESPP and we
    reserved an additional <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_58982d3bd4cb40b3bbb0b5a03017f488" contextRef="c20090101to20091231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">150,000</ix:nonFraction> shares of common stock for issuance thereunder. In each of the subsequent years until 2019, we reserved an
    additional <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_e15dcdc6c66e42559a10c287b0c7cf55" contextRef="c20180101to20181231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_cacfad7964034bbcaca2399bf5f2cb59" contextRef="c20150101to20151231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_c4b9f36e104042d497da7d7c2821b9f9" contextRef="c20140101to20141231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_c241e58357d3452dbf7f5a5a59d22102" contextRef="c20130101to20131231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_a4221b1732584bdab68ea669d5dbfe57" contextRef="c20110101to20111231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_9d75e90a44af478cbe373b16a80b30bf" contextRef="c20190101to20191231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_55052c57d9944f4597bc1762f9393ed7" contextRef="c20170101to20171231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_465d86e4aca54bf99fa8576d3a113eb5" contextRef="c20160101to20161231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_1a5a7e2d42b24fe5bbdd8eb2e9ed40a3" contextRef="c20120101to20121231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_199329985b3f4b9a93a30c0aba085d4e" contextRef="c20100101to20101231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">150,000</ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction> shares of common stock for the ESPP resulting in a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_38cefc5306ef4b91b96aa796ece9f65c" contextRef="c20241231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.2</ix:nonFraction> million shares authorized under the plan as of December 31, 2024.
    The ESPP permits full-time employees to purchase common stock through payroll deductions (which cannot exceed <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" id="Fact_cde6d0b8308541d399ef173d781f45db" contextRef="c20241231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">10</ix:nonFraction> percent of each employee&#8217;s
    compensation) at the lower of <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" id="Fact_194baea1b26142beaba2816576b72b95" contextRef="c20240101to20241231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">85</ix:nonFraction> percent of fair market value at the beginning of the purchase period or the end of each purchase period. Under
    the amended and restated ESPP, employees must hold the stock they purchase for a minimum of <ix:nonNumeric name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" id="Fact_c0a6d71bb09f40b8b835538d12005c8d" contextRef="c20240101to20241231_PlanNameAxis_EmployeeStockPurchasePlanMember" format="ixt-sec:durwordsen">six months</ix:nonNumeric> from the date of purchase. During 2024, employees purchased and we issued to employees <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" id="Fact_28531580c1b34f999f1b8c754d078864" contextRef="c20240101to20241231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction>
    million shares under the ESPP at a weighted average price of $<ix:nonFraction name="ions:EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" id="Fact_19161be6484c4f6f96fdfb2dbfaf9342" contextRef="c20240101to20241231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">35.93</ix:nonFraction> per share. At December 31, 2024, there were <ix:nonFraction name="ions:EmployeeStockPurchasePlanSharesAvailableForPurchase" id="Fact_d43712676b7c40d4972a35e470cb8c41" contextRef="c20241231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.3</ix:nonFraction> million shares available for
    purchase under the ESPP.</div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce61" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce62">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce62" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce63">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock Option Activity</div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce63" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce64">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce64" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce65"><ix:nonNumeric name="us-gaap:ScheduleOfShareBasedCompensationStockOptionsActivityTableTextBlock" id="Text_b08686db7e214f558296c6c15bcdf2af" contextRef="c20240101to20241231" escape="true" continuedAt="Text_0c3ebbd9ab4e402eb9b36a155efe8e561">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the stock option activity under our stock plans for the year ended December 31, 2024 (in thousands, except per share and contractual life data):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce65" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce66"><ix:continuation id="Text_0c3ebbd9ab4e402eb9b36a155efe8e561" continuedAt="Text_0c3ebbd9ab4e402eb9b36a155efe8e562">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce66" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce67"><ix:continuation id="Text_0c3ebbd9ab4e402eb9b36a155efe8e562">
<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

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    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Exercise</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Price Per Share</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Remaining</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contractual Term</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Years)</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Aggregate</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intrinsic</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Outstanding at December 31, 2023</span></div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_de361e6a303f48689eff997a4c7a9e18" contextRef="c20231231_AwardTypeAxis_StockOptionMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,091</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" id="Fact_147bf3d775c544d39301adb1493fa05e" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">49.77</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exercised</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesStockOptionsExercised" id="Fact_65fe49e661654c6fadd66c3158cb37e5" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">399</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice" id="Fact_645eac997a48446a8364fedf6f9b00a2" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">39.55</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited/expired</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" id="Fact_d7093d8852d44af280644f5b3f4724f8" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,704</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; padding-bottom: 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice" id="Fact_b2d99eaaf66c4310b3826984e917430d" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">54.40</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Outstanding at December 31, 2024</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_ac7cb8c9588948168b54c219f469e752" contextRef="c20241231_AwardTypeAxis_StockOptionMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,717</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" id="Fact_3a779dec16434ab39ded18c995252583" contextRef="c20241231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">48.23</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" id="Fact_8a97634ee0de48ab9bba7815890a31ce" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" format="ixt-sec:duryear">5.27</ix:nonNumeric></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" id="Fact_c25c76c1a9f94691b856964b458fadef" contextRef="c20241231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,692</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Exercisable at December 31, 2024</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_f87605af70314ee88af627c71f1097ba" contextRef="c20241231_AwardTypeAxis_StockOptionMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,089</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" id="Fact_385eca89102d4e9587c5000cc39964b4" contextRef="c20241231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">49.85</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" id="Fact_7314f310e53045fd9d6e985a8a4eb55d" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" format="ixt-sec:duryear">3.66</ix:nonNumeric></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1" id="Fact_bb850db7a9184d57b61549c6a8eeacca" contextRef="c20241231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,460</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

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</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The weighted-average estimated fair values of options granted were $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_bd436c790ccc47e68cd7e2153d0e63dd" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">24.37</ix:nonFraction>, $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_4dd2a593ab554175bbb0a93d55390a88" contextRef="c20230101to20231231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">19.72</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_a3befa246b7c4d03aced2b483085120f" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">18.66</ix:nonFraction> for the years ended December 31, 2024, 2023 and 2022, respectively. The total
    intrinsic value of options exercised during the years ended December 31, 2024, 2023 and 2022 were $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_1218d40eea68418bb4f00f1ad78f4cff" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.6</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_bde2c92764604d8497b0668d13fb888b" contextRef="c20230101to20231231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.0</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_8cc0e16daa8e4b2382fc554cc98ddf99" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.4</ix:nonFraction> million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $<ix:nonFraction name="us-gaap:ProceedsFromStockOptionsExercised" id="Fact_83423df31a3f436fab220d64f20b3ada" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">15.8</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ProceedsFromStockOptionsExercised" id="Fact_9199ba163c904e0aaa3d539cccdda650" contextRef="c20230101to20231231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">65.1</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ProceedsFromStockOptionsExercised" id="Fact_6cc972e2025849d8a6820145ab793c87" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.6</ix:nonFraction> million for the years ended December 31, 2024, 2023 and 2022, respectively. For the year
    ended December 31, 2024, the weighted-average fair value of options exercised was $<ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" id="Fact_2b17593a26f3421991429bedce8b1c41" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">48.59</ix:nonFraction>. As of December 31, 2024, total unrecognized compensation cost
    related to non-vested stock options was $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" id="Fact_72c37b7b47114b45a9abf8d6722faa52" contextRef="c20241231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">43.7</ix:nonFraction> million. We expect to recognize this cost over a weighted average period of <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_b3913cf410e541fe90a6f1003271ba18" contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember" format="ixt-sec:duryear">1.1</ix:nonNumeric> years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.</div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-39</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Restricted Stock Unit Activity</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the RSU activity for the year ended December 31, 2024 (in thousands, except per share data):</div>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Grant Date Fair</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value Per Share</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2023</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" id="Fact_9b79ad26dfed4644a99778a07c2788e7" contextRef="c20231231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,239</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" id="Fact_7b0c381469384de4a83c2d06c591c7e0" contextRef="c20231231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">43.40</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" id="Fact_1bdc071fcc1b43c49a958a8b0de0d593" contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,005</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_029b251fe1ed4825bb24ef350c208693" contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">50.92</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" id="Fact_32f1bead9c704269b614ad1cd037ad04" contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,185</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" id="Fact_df38f96941f0458f9ca876b79bbed1b6" contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">46.88</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod" id="Fact_22694e1383774415bf4c78c2ec3ee1f6" contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">228</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" id="Fact_d3684b8ecd434d79a0c627293baaf219" contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">46.83</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2024</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;">
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</table>
</ix:continuation></ix:continuation>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce76" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce77">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024,
    2023 and 2022, the
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</ix:continuation>
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<div><br/>
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  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce78" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce79">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Performance Restricted Stock Unit Activity</div>
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<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the PRSU activity for the year ended December 31, 2024 (in thousands, except per share data):</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
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</ix:continuation></ix:continuation>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value Per Share</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

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          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2023</span></div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" id="Fact_89dc0084c002439b8e4a0538481494ee" contextRef="c20231231_AwardTypeAxis_PerformanceSharesMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">56.04</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" id="Fact_8872b93150d3431d9d42102aaf351b3e" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">179</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_e98c02aa77564502bd9487c4f288a2e3" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">78.41</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" id="Fact_f9eaab21668f41b3800f1ff2a0297f69" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">73</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" id="Fact_0e0561a01e9042e689b1dc7f1a864cf8" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">53.35</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod" id="Fact_e25be1b0ba6b4b1d8aec4cd1a7139005" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">25</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" id="Fact_6f180152de9a4c9987eee264a2504267" contextRef="c20240101to20241231_AwardTypeAxis_PerformanceSharesMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">68.21</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2024</span></div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" id="Fact_906d40767f024bc590b3fab48a78fe59" contextRef="c20241231_AwardTypeAxis_PerformanceSharesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">307</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" id="Fact_8d1f45fc49f745769240429abaa6978d" contextRef="c20241231_AwardTypeAxis_PerformanceSharesMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">66.72</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce83" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce84">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce84" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce85">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024,
    2023 and 2022, the
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-based Compensation Expense and Valuation Information</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the years ended December 31, 2024, 2023 and 2022 (in thousands):</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_fbf019d0d38c4d20951785656bdfb76e" contextRef="c20230101to20231231_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">77,826</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_590dd7d3580e4ce79e0bd853a27c60e2" contextRef="c20220101to20221231_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">73,704</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_faf4608623c94854a015ec45e8a2e44a" contextRef="c20240101to20241231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">37,030</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_e2891cabb204471380d6c8707ca7c311" contextRef="c20230101to20231231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,484</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_1d43b8c463a34284a11803d822ccf283" contextRef="c20220101to20221231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">26,027</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense, net of amounts capitalized</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_e526ced9a8ee48df88cdbb0fe414de86" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">130,200</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_e09ed4e35f1149ffade548f4d1e3dd6a" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">105,809</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_14e48c9e15754897b6ddb6e8ce984ffb" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">100,264</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Capitalized stock-based compensation expense</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" id="Fact_4bf3f44d108a47ab8d8d5b80c3d6254f" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">799</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" id="Fact_71582b5bee0d424fb95b9cfa2abe6096" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" id="Fact_e182892098e64cff94597171884b2976" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stock-based compensation expense</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" id="Fact_fd032fbf1bc64eebb3e15e92b7d464c8" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">130,999</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" id="Fact_6fffbc8e74fe46369fbad2107d1965cb" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">105,809</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" id="Fact_2e4de6a2ab764dc990d943ad6737f626" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">100,264</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense increased in 2024 compared to 2023 due to increased headcount and a higher stock price on the grant date
    of annual equity awards in 2024 compared to 2023. Refer to Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span>, for further details on how we
    determine the fair value of stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP.</div>
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<div><br/>
  </div>
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  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-40</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024,
    2023 and 2022, we used the
    following weighted-average assumptions in our Black-Scholes calculations:</div>
</ix:continuation>

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<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Options:</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_6f0bd71680af49fe8c31973636909b08" contextRef="c20230101to20231231_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.0</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_467f22edbb03445faa1bf91c44625ca8" contextRef="c20220101to20221231_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.0</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_e343e701b7bb4973a553dcb0d627618e" contextRef="c20240101to20241231_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">43.7</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_cf083492bd334305a8d635507396630c" contextRef="c20230101to20231231_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">46.8</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_b479bbaa6e5942498c2c6ef23bade12e" contextRef="c20220101to20221231_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">54.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_aeba017ee0304164a606372e31b4d36e" contextRef="c20240101to20241231_AwardTypeAxis_EmployeeStockOptionMember" format="ixt-sec:duryear">6.3</ix:nonNumeric> years</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_4ff009d529b14f28a67b413d0aa72b8a" contextRef="c20230101to20231231_AwardTypeAxis_EmployeeStockOptionMember" format="ixt-sec:duryear">6.3</ix:nonNumeric> years</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_17b6c1af49ea4548aea7024e13340b1f" contextRef="c20220101to20221231_AwardTypeAxis_EmployeeStockOptionMember" format="ixt-sec:duryear">6.3</ix:nonNumeric> years</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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<div><br/>
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce100" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce101"><ix:continuation id="Text_433277ceb9ef4ea89c9578b78fb705fe4" continuedAt="Text_433277ceb9ef4ea89c9578b78fb705fe5">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Board of Director Stock Options:</div>
</ix:continuation></ix:continuation>
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<div><br/>
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce102" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce103"><ix:continuation id="Text_433277ceb9ef4ea89c9578b78fb705fe6">
<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

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    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" id="Fact_7e683d90439c433b952d511d85e1a926" contextRef="c20220101to20221231_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">1.2</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_0eb7e7fbc4304fdf9099a8b950d12dde" contextRef="c20230101to20231231_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.0</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_34e237d15deb4d56bee7e4f7c1e34d34" contextRef="c20220101to20221231_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.0</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_9ae61ebbc4da40a487b4fb949bf8e04a" contextRef="c20230101to20231231_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">36.0</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_46d7ebf746c644dbab44800478c4bf2c" contextRef="c20220101to20221231_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">50.1</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_6cb5a0bf099e40cc864c264a7ce21cef" contextRef="c20240101to20241231_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durwordsen">6 months</ix:nonNumeric></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_f4dc66b6347f46f7b1f589a4102dcbc3" contextRef="c20230101to20231231_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durwordsen">6 months</ix:nonNumeric></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_b50f67a3f15a4f28a7f815371d6feb14" contextRef="c20220101to20221231_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durwordsen">6 months</ix:nonNumeric></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce108" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce109">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk-Free Interest Rate.</span> We base
    the risk-free interest rate assumption on observed interest rates appropriate for the term of our stock option plans or ESPP.</div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce109" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce110">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce110" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce111">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Dividend Yield.</span> We base the
    dividend yield assumption on our history and expectation of dividend payouts. We have not paid dividends in the past and do not expect to in the future.</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce112" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce113">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Volatility.</span> We use an average of
    the historical stock price volatility of our stock for the Black-Scholes model. We computed the historical stock volatility based on the expected term of the awards.</div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce113" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce114">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce114" continuedAt="Text_29f34bda8bb243ffae7fa41f7742acce115">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Expected Life. </span>The expected term
    of stock options we have granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options we have granted based on actual and projected exercise patterns. In 2021, our Compensation
    Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options granted under these plans from <span style="-sec-ix-hidden:Fact_bd3d24dad695460d8e7018466f08295c"><span style="-sec-ix-hidden:Fact_a0ee4419d26449d89aee22da843bd7ad">seven</span></span> to <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_ca599c0bec514341bfbc694c29062946" contextRef="c20240101to20241231_AwardDateAxis_IssuedAfterDecember312021Member_AwardTypeAxis_EmployeeStockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_c4148e9887894ea9af96e0d8258b9049" contextRef="c20240101to20241231_AwardDateAxis_IssuedAfterDecember312021Member_AwardTypeAxis_EmployeeStockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">ten years</ix:nonNumeric></ix:nonNumeric> for stock options granted on January 1, 2022
    and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other
    means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the years ended December 31, 2024, 2023 and 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical
    information, we will transition to calculating our expected term based on our historical exercise patterns.</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_29f34bda8bb243ffae7fa41f7742acce116">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Forfeitures.</span> We reduce stock-based
    compensation expense for estimated forfeitures. We estimate forfeitures at the time of grant and revise, if necessary, in subsequent periods if actual forfeitures differ from those estimates. We estimate forfeitures based on historical experience. </div>
</ix:continuation></div>

  <div><br/>
  </div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-41</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
<div><ix:nonNumeric name="us-gaap:IncomeTaxDisclosureTextBlock" id="Text_6df02471ad074e68b7de0becddf8a447" contextRef="c20240101to20241231" escape="true" continuedAt="Text_c0124f59f96f4430926b04e674831d3c1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">9. Income Taxes</div>
</ix:nonNumeric>

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  <ix:continuation id="Text_c0124f59f96f4430926b04e674831d3c2" continuedAt="Text_c0124f59f96f4430926b04e674831d3c3"><ix:nonNumeric name="us-gaap:ScheduleOfIncomeBeforeIncomeTaxDomesticAndForeignTableTextBlock" id="Text_7281bd0eb54443b994694c659a6a8f66" contextRef="c20240101to20241231" escape="true" continuedAt="Text_78e63a52e1c344389d4b6e32525c0ca51">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss before income taxes is comprised of (in thousands):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_c0124f59f96f4430926b04e674831d3c3" continuedAt="Text_c0124f59f96f4430926b04e674831d3c4"><ix:continuation id="Text_78e63a52e1c344389d4b6e32525c0ca51" continuedAt="Text_78e63a52e1c344389d4b6e32525c0ca52">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic" id="Fact_1154d9477ea5403c89bcaba61b591e79" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">460,712</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic" id="Fact_74d3abad4f744e0aa68801acc3a6ed6b" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">334,707</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic" id="Fact_8977ca2c8272434794efd8259c5f22b7" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">258,493</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign" id="Fact_70ca994a31be49619caefe5e71de1587" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">644</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign" id="Fact_8425f2adaf6948cdb4db61cdf7def1fc" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">742</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign" id="Fact_15eeca6092a14a5c9b839eb716ea8ae4" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">508</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss before income taxes</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
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  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_c0124f59f96f4430926b04e674831d3c5" continuedAt="Text_c0124f59f96f4430926b04e674831d3c6">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our income tax expense (benefit) was as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
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</ix:continuation></ix:continuation>
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Federal</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CurrentFederalTaxExpenseBenefit" id="Fact_f7d1c022ad9f48ddaa94094db5e10a09" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">5,492</ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentFederalTaxExpenseBenefit" id="Fact_7390edee7ebc486d8f38622d5c52bcc1" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,522</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CurrentStateAndLocalTaxExpenseBenefit" id="Fact_18598915ff304ad69c4f603530fa17ba" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">3,687</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentStateAndLocalTaxExpenseBenefit" id="Fact_b16b487bd08b4f16b0833b9f760c9124" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,129</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentForeignTaxExpenseBenefit" id="Fact_ca5d84cba52a406991333d46438a92be" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">169</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentForeignTaxExpenseBenefit" id="Fact_7ac2061535c24653b193dc9c25179163" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">147</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentForeignTaxExpenseBenefit" id="Fact_94c31631758a4c52bc819107405e16bf" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">86</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current income tax expense (benefit)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CurrentIncomeTaxExpenseBenefit" id="Fact_273269185dee42eb91195045f6449fc7" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">6,171</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentIncomeTaxExpenseBenefit" id="Fact_33a16e765b9c499ba27c595254ef3547" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,321</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentIncomeTaxExpenseBenefit" id="Fact_2d44830595d442f082fda176f5b4c723" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Federal</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredFederalIncomeTaxExpenseBenefit" id="Fact_c00a5eec073e447cab0567a91678c321" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredStateAndLocalIncomeTaxExpenseBenefit" id="Fact_e78064ae2d4443f18407baa35f73bf2f" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredStateAndLocalIncomeTaxExpenseBenefit" id="Fact_d254df8f11b14f8594ca47e6a7f95134" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total deferred income tax benefit</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxExpenseBenefit" id="Fact_be2ed18e2072458bba8c88d0a45981b5" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxExpenseBenefit" id="Fact_499db25413694d1996ce63465160cf19" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxExpenseBenefit" id="Fact_b02665644bb848b5b79ed1b9b7aba937" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total income tax expense (benefit)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_39aa3556afa54b90a94840a97eb5b995" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">6,171</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_d3a17d5cbd604f2eaffbec171dab238a" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,321</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_72e6d39ff1da4d90b52e886f5e5ff672" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_c0124f59f96f4430926b04e674831d3c9" continuedAt="Text_c0124f59f96f4430926b04e674831d3c10">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_c0124f59f96f4430926b04e674831d3c10" continuedAt="Text_c0124f59f96f4430926b04e674831d3c11"><ix:nonNumeric name="us-gaap:ScheduleOfEffectiveIncomeTaxRateReconciliationTableTextBlock" id="Text_51a6178b5d104096a200807a70958787" contextRef="c20240101to20241231" escape="true" continuedAt="Text_51707f632a6740528a444a853c6547a41">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to loss before income taxes. The sources
    and tax effects of the differences are as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_c0124f59f96f4430926b04e674831d3c11" continuedAt="Text_c0124f59f96f4430926b04e674831d3c12"><ix:continuation id="Text_51707f632a6740528a444a853c6547a41" continuedAt="Text_51707f632a6740528a444a853c6547a42">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_c0124f59f96f4430926b04e674831d3c12" continuedAt="Text_c0124f59f96f4430926b04e674831d3c13"><ix:continuation id="Text_51707f632a6740528a444a853c6547a42">
<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="22" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pre-tax loss</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_48c8db752dd847f894945e665263db28" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">460,068</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_d90962261a1d4e50b88595c178ff0d7d" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">333,965</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_82f7c2373f9d4876bd0497532436a6c4" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">257,985</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxReconciliationForeignIncomeTaxRateDifferential" id="Fact_a8b08aa07f334b19ae749ec79bb4c2f8" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">49</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential" id="Fact_3073dd31dd784f6199bcbd4645c6a2c9" contextRef="c20220101to20221231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.0</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net change in valuation allowance</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax rate change</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-deductible compensation</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent" id="Fact_8a1f4cfd47914ffdbf619fcbc8052f31" contextRef="c20240101to20241231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">0.4</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount" id="Fact_c63d7e7b9487406bac497ca46a6fc820" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,814</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount" id="Fact_c2fa1635eae94d73911269398d313a08" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,023</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent" id="Fact_5755b6fed27041f187a7d0f88f7107ea" contextRef="c20220101to20221231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">1.2</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other non-deductible items</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationNondeductibleExpenseOther" id="Fact_d3f365ea019845c7bf004cde11c47f07" contextRef="c20240101to20241231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.0</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationFdiiPercent" id="Fact_f35de3ad242445479bb8e21f8cff17f0" contextRef="c20230101to20231231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">2.2</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost" id="Fact_896722cf23bd46bd892c4514b440f82b" contextRef="c20240101to20241231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">2.3</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost" id="Fact_4ace56cd661941dda164a7b4d1dbc5d5" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">19,546</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost" id="Fact_883950498a674a698da46bd68262d2a9" contextRef="c20230101to20231231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">5.9</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost" id="Fact_72b2dcbbe49449748e7c9c75562444f6" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,030</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost" id="Fact_9e38310d67c54659ba2147167a59a001" contextRef="c20220101to20221231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">5.4</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxReconciliationOtherAdjustments" id="Fact_579c7a65442043da929eea96c26a5f30" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">665</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationOtherAdjustments" id="Fact_d4daf54210844f62bbb1a04059ef74aa" contextRef="c20240101to20241231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">0.2</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxReconciliationOtherAdjustments" id="Fact_a992f73d15204a0081e6aa41357a8de5" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">401</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationOtherAdjustments" id="Fact_4c434cf931ee4c45825ee90aa9c5caf0" contextRef="c20230101to20231231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.1</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxReconciliationOtherAdjustments" id="Fact_bc52c68679ef48cab49f85908463be0f" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">344</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationOtherAdjustments" id="Fact_4d88b363955f43e1a07814eb57337204" contextRef="c20220101to20221231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">0.1</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective rate</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_deca3f5e839941f4a90d3b8031b558aa" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">6,171</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateContinuingOperations" id="Fact_5b3403b4768d4be492d67b3c92d9483d" contextRef="c20240101to20241231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">1.3</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_9706d35248bb454c8a3a3c80240bc33f" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,321</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateContinuingOperations" id="Fact_f0cc7188c05e4808b694a7a38a1291cc" contextRef="c20230101to20231231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">9.7</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_05f18d362e2441e2a636fa371d9e87f0" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateContinuingOperations" id="Fact_b6d022290a824526a58ab495c81c8422" contextRef="c20220101to20221231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">4.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>


</table>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred income taxes reflect the net tax effects of temporary differences between the carrying amounts of assets and liabilities for
    financial reporting purposes and the amounts used for income tax purposes.</div>
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<div><br/>
  </div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-42</div>

    </div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
<div><ix:continuation id="Text_c0124f59f96f4430926b04e674831d3c16" continuedAt="Text_c0124f59f96f4430926b04e674831d3c17"><ix:nonNumeric name="us-gaap:ScheduleOfDeferredTaxAssetsAndLiabilitiesTableTextBlock" id="Text_95c40f8276904e2fae4df346cec44c24" contextRef="c20240101to20241231" escape="true" continuedAt="Text_ed2c038037c44ccbb0b3fee538d1e9f81">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Significant components of our deferred tax assets and liabilities as of December 31, 2024 and 2023 are as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation>

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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred Tax Assets:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net operating loss carryovers</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsOperatingLossCarryforwards" id="Fact_f6113dec90244be7a15feeec0e7f99b3" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">95,851</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsOperatingLossCarryforwards" id="Fact_de531fc8054a467eb0d8ebe192e75809" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">77,964</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax credits</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsTaxCreditCarryforwards" id="Fact_6e4434c808b24cdd8e98c8c527eccd87" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">310,703</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsTaxCreditCarryforwards" id="Fact_8cae73daf0c14e699722d8495d504e3f" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">239,962</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred revenue</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsDeferredIncome" id="Fact_3161a0571c2d40cfa484d6df3f0587b3" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">54,063</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsDeferredIncome" id="Fact_8e7b04eb5d41408cb9a2aae8c76b704c" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">71,683</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost" id="Fact_cf4d0af63f314ebebc4008a2387ff7ba" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">82,660</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost" id="Fact_616f9b6b59aa4b9b83a42abbfc396399" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">77,468</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intangible and capital assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsGoodwillAndIntangibleAssets" id="Fact_1eb4e0ee7798484c84a06c938cd4969a" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">93,541</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsGoodwillAndIntangibleAssets" id="Fact_5dbb3a06f1ce4e86bcf8b0b23175d4c6" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">104,380</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible debt</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsFinancingArrangements" id="Fact_d5e56b516fd44b23a7d77df2c87dd193" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,310</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsFinancingArrangements" id="Fact_56e973c6c9d8438697c10963c3e2b910" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,849</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Capitalized research and development expenses</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" id="Fact_7552c538820b415fa183b42f515e84f9" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">323,560</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" id="Fact_454847e0096740a1b60db473f3a38457" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">238,738</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term lease liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsLeasingArrangements" id="Fact_f1bc5ca109b2461198124e062adb4830" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">41,481</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsLeasingArrangements" id="Fact_21b8f2ff8dfe4306a563b7b9403bb6ad" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">43,718</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sale of future royalties</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsSaleOfFutureRoyalties" id="Fact_dbb07f37125e48fcb324ad5b7b909a70" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">148,918</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsSaleOfFutureRoyalties" id="Fact_b3acd3b9b3474c74b270c8e16b14119e" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">144,608</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsOther" id="Fact_68255c3bd980428f8ac1596cf0f40278" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,024</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsOther" id="Fact_8fd4dba767ea4fb1ad2e077d22dd1144" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,343</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total deferred tax assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsGross" id="Fact_db490d6be6234997ab204f135fae4219" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,174,111</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsGross" id="Fact_0e07da67ce43444f913fc9c18171c638" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,025,713</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred Tax Liabilities:</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Fixed assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesPropertyPlantAndEquipment" id="Fact_e25b4841ea8643daaead657546cec52e" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,719</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesPropertyPlantAndEquipment" id="Fact_9878485dcb08467684a2d157588eeafd" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,166</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use assets</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesLeasingArrangements" id="Fact_0d69436048d84a5eb26b450649e27a54" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">36,788</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesLeasingArrangements" id="Fact_f621ee4c764a4d53b8a656ccc5cb49f9" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">42,007</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesOther" id="Fact_1b5703c2c4764515a3e8ad2afeea59cf" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,896</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesOther" id="Fact_1b2f279a0c764ac6861cf53127c15459" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,910</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net deferred tax asset</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" id="Fact_2aed2e8242ea4d2a953befcd5fd869ee" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,129,708</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" id="Fact_079ce9450c7a4660ba7391c5cb7a50dc" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">977,630</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Valuation allowance</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxAssetsValuationAllowance" id="Fact_972868dc5873412980ceca72fd836c11" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,129,708</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxAssetsValuationAllowance" id="Fact_2c9b12b4481545a7ba60367cdb421919" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">977,630</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total net deferred tax assets and liabilities</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsLiabilitiesNet" id="Fact_57658da53796431d95347a5ae91df615" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsLiabilitiesNet" id="Fact_b0ad9b5a1bcf4171839877e1f6c48962" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_c0124f59f96f4430926b04e674831d3c19" continuedAt="Text_c0124f59f96f4430926b04e674831d3c20">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_c0124f59f96f4430926b04e674831d3c20" continuedAt="Text_c0124f59f96f4430926b04e674831d3c21">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024, we maintained a full valuation allowance on our net deferred tax assets. We determined the valuation allowance in
    accordance with the provisions of ASC 740, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Accounting for Income Taxes</span>, which requires an assessment of both positive and negative evidence when
    determining whether it is more likely than not that deferred tax assets are realizable. Our recent history of cumulative losses and expected near-term future losses require us to record a full valuation allowance against all net deferred tax assets. We
    will maintain a full valuation allowance on net deferred tax assets until sufficient positive evidence exists to support reversal of the valuation allowance<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our valuation allowance increased by $<ix:nonFraction name="us-gaap:ValuationAllowancesAndReservesPeriodIncreaseDecrease" id="Fact_66c86cbe348d4776a343b6ddac2f20fe" contextRef="c20240101to20241231" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">152</ix:nonFraction>
    million from December 31, 2023 to December 31, 2024.
    The increase was primarily related to increases in our deferred tax assets for capitalized research and development expenses and tax credits.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2024, we had
    federal and state, primarily California, tax net operating loss carryforwards of $<ix:nonFraction name="us-gaap:OperatingLossCarryforwards" id="Fact_d9f8be4484bf4eb29dfdbd375c201523" contextRef="c20241231_IncomeTaxAuthorityAxis_DomesticCountryMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">290.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLossCarryforwards" id="Fact_ad3cae48e06445f7aefbd80a218590f4" contextRef="c20241231_IncomeTaxAuthorityAxis_StateAndLocalJurisdictionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">526.9</ix:nonFraction> million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2032. At December 31, 2024, we also had federal and California research and development tax credit carryforwards of $<ix:nonFraction name="us-gaap:TaxCreditCarryforwardAmount" id="Fact_895e697c597d405a96e760deb75e2c01" contextRef="c20241231_IncomeTaxAuthorityNameAxis_InternalRevenueServiceIRSMember_TaxCreditCarryforwardAxis_ResearchMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">234.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:TaxCreditCarryforwardAmount" id="Fact_8191e961253a4f2faaff06f7920ca14f" contextRef="c20241231_IncomeTaxAuthorityNameAxis_CaliforniaFranchiseTaxBoardMember_TaxCreditCarryforwardAxis_ResearchMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">137.6</ix:nonFraction> million, respectively. Our federal research and
    development tax credit carryforwards will begin to expire in 2037. Our California research and development tax credit carryforwards are available indefinitely.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Utilization of the net operating loss and tax credit carryforwards may be subject to an annual limitation due to the ownership change
    limitations provided by the Internal Revenue Code of 1986, as amended, and similar state provisions. The annual limitation may result in the expiration of net operating losses and credits before utilization.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We analyze filing positions in all U.S. federal, state and foreign jurisdictions where we file income tax returns, and all open tax years
    in these jurisdictions to determine if we have any uncertain tax positions on any of our income tax returns. We recognize the impact of an uncertain tax position on an income tax return at the largest amount that the relevant taxing authority is
    more-likely-than not to sustain upon audit. We do not recognize uncertain income tax positions if they have less than 50 percent likelihood of the applicable tax authority sustaining our position.</div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-43</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our gross unrecognized tax benefits <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(in thousands):</span></div>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance of unrecognized tax benefits</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_6f5ba375963f47a19fbb04fed7232165" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">43,298</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_0f12ba3f88584d21bf0b87b613d47847" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">56,567</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_67e334d942db4ea29c0cbe3ffcea2715" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">55,085</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Decrease for lapse of statute of limitations</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations" id="Fact_250dd0d51f724c849bf2036b1a2903c8" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,579</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations" id="Fact_173d579361214e7b8c8d89c6f00bbbb0" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,993</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations" id="Fact_6152a6544b8f4685b14436ee97f6ce58" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Decrease for prior period tax positions</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" id="Fact_3f06e5d0f5b747c280280e9fcf69a448" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">110</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" id="Fact_39287cd4b49c44a4a617144fa53df1bf" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">737</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" id="Fact_0bb19795798b4cca8d22978a26340bd0" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">267</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for prior period tax positions</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" id="Fact_ecf1724d9d65437ab5ccd486d8ab6ebd" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,902</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" id="Fact_0ad407c0955648c48850ba2d8d052462" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">429</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" id="Fact_7d0ea3f6a325421b85ab3cbb04eb12fa" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">259</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for current period tax positions</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" id="Fact_6119186f5d854118b836ddc5c481ef2d" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,650</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" id="Fact_f3e7b13433a84e72a642c54ecc6a02b3" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,032</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" id="Fact_809af95107674a60b9a6aa50165e5ba7" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,490</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance of unrecognized tax benefits</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_c2747640a25a483791181f56caf8bc45" contextRef="c20241231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">41,161</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_58382ea6463045ef8f7cefb3fdbf3dd7" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">43,298</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_ed1574437d194d92b955e24fdec9efce" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">56,567</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


</table>
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  </div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in the balance of unrecognized tax benefits at December 31, 2024, 2023 and 2022 was $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" id="Fact_552285171ef248dfab36d0ee9948271e" contextRef="c20241231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.3</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" id="Fact_609bbfafde0b4ea9bce0bad6399c9eb6" contextRef="c20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.3</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" id="Fact_49d7f6eb2570409abc1312c432abdfe0" contextRef="c20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.2</ix:nonFraction> million respectively, that if we recognized, could
    impact our effective tax rate, subject to our remaining valuation allowance.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any material changes to our gross unrecognized tax benefits within the next 12 months.</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize interest and/or penalties related to income tax matters in income tax expense. During the years ended December 31, 2024, 2023 and 2022, we recognized $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_5d817f0050924f7f82257fc7b70a23d7" contextRef="c20240101to20241231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_2955ef1a6fab40d7ab1c8f70571532db" contextRef="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_8781f6db0d834e54aff079e85ee20d63" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.8</ix:nonFraction> million, respectively, of
    accrued interest and penalties related to gross unrecognized tax benefits.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are subject to taxation in the U.S. and various state and
      foreign jurisdictions. U.S. tax years 2021 through 2023 remain open to examination and tax years 2020 through 2023 remain open to examination by major state taxing jurisdictions, primarily California, although net operating loss and credit
      carryforwards generated prior to these periods may still be adjusted upon examination by the Internal Revenue Service or state tax authorities if they have been used in an open period or are used in a future period</span>.</div>
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  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting guidance for income taxes requires a deferred tax liability to be established for the tax impact of undistributed earnings of
    foreign subsidiaries unless it can be shown that these earnings will be permanently reinvested outside the U.S. If our foreign earnings were to be repatriated in the future, the estimated tax liability would be insignificant.</div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:PensionAndOtherPostretirementBenefitsDisclosureTextBlock" id="Text_44a1974bfba9485682c02d2913778f03" contextRef="c20240101to20241231" escape="true" continuedAt="Text_54d8bb93626049daa0f7f16a5fa11d671">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">10. Employment Benefits</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have employee 401(k) salary deferral plans covering all employees. Employees could make contributions by withholding a percentage of
    their salary up to the IRS annual limits of $<ix:nonFraction name="us-gaap:DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" id="Fact_06c142c7ec1040e0b05c4b2596dfe112" contextRef="c20240101to20241231_RangeAxis_MinimumMember" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">23,000</ix:nonFraction> and $<ix:nonFraction name="us-gaap:DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" id="Fact_2703ad6213db4e249c38d0794a2c6418" contextRef="c20240101to20241231_RangeAxis_MaximumMember" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">30,500</ix:nonFraction> in 2024 for employees under 50 years old and employees 50 years old or over, respectively. We made
    approximately $<ix:nonFraction name="us-gaap:DefinedContributionPlanCostRecognized" id="Fact_345fd7748408424580894d7cb0e0e108" contextRef="c20240101to20241231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.6</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:DefinedContributionPlanCostRecognized" id="Fact_47a2898dc66b4221ba3a2d92c2c0643a" contextRef="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.1</ix:nonFraction>
    million and $<ix:nonFraction name="us-gaap:DefinedContributionPlanCostRecognized" id="Fact_0c0b367e1550466b886c0390a13e1e0f" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.6</ix:nonFraction> million in matching contributions for the years ended December 31, 2024, 2023 and 2022, respectively.</div>
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  <div><br/>
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<div><ix:nonNumeric name="us-gaap:LegalMattersAndContingenciesTextBlock" id="Text_656730b2a28e4e958b751e639ff66fd5" contextRef="c20240101to20241231" escape="true" continuedAt="Text_eeff14c2915e45de989243c5e9420a5f1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">11. Legal Proceedings</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the
    status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of
    any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the
    amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are no pending material legal proceedings to which we are a party or of which our property is the subject.</div>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">F-44</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#TOC" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Table of Contents</a></div>

    </div>

  </div>
<div><ix:nonNumeric name="us-gaap:SegmentReportingDisclosureTextBlock" id="Text_fbf9a7cc665b405c8fc8a906a61d8c8c" contextRef="c20240101to20241231" escape="true" continuedAt="Text_8542231756644ea1b083eea3b0fb605b1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">12. Segment Information</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We operate as a <span style="-sec-ix-hidden:Fact_2519ca12728c45f9b7af0ac92fa19388">single</span>
    operating segment, Ionis operations, focused on the research, development and commercialization of our RNA-targeted medicines to bring better futures to people with serious diseases. As the CODM, our Chief Executive Officer manages our company, reviews
    operating results, assesses performance and allocates resources on an aggregate basis using consolidated net income or loss as the key measure of segment profit or loss. As such, results of our operations are reported on a consolidated basis for
    purposes of management and segment reporting.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis operations derives its revenues from commercial and R&amp;D revenue sources. Refer to Note 3, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenues</span>, for further details on our sources of revenue.</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on segment profit or loss, including significant segment expenses (in thousands):</div>
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<table cellspacing="0" cellpadding="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"> </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less:</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostOfGoodsAndServicesSold" id="Fact_bfe66dcbe9504985938167a760311944" contextRef="c20240101to20241231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,415</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostOfGoodsAndServicesSold" id="Fact_bab17944de934de39618fd6ce863846c" contextRef="c20230101to20231231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,686</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostOfGoodsAndServicesSold" id="Fact_a84d6be026fc411b9c873b94f992c41a" contextRef="c20220101to20221231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">13,447</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug discovery</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DrugDiscoveryExpenses" id="Fact_948768d308874846b3ed04e0d5f3e12d" contextRef="c20240101to20241231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">114,350</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DrugDiscoveryExpenses" id="Fact_9791c80d3a9e42d18b49d2e507f3fc4e" contextRef="c20230101to20231231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">125,649</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DrugDiscoveryExpenses" id="Fact_48f33d2077204a51b1287f9bb1fae57a" contextRef="c20220101to20221231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">181,302</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug development</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DrugDevelopmentExpenses" id="Fact_90efbc3c55cd4b7085d85d7575629a74" contextRef="c20240101to20241231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">527,259</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DrugDevelopmentExpenses" id="Fact_7ff1224b2f1b4fd5ab25ac721035a4cb" contextRef="c20230101to20231231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">530,332</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DrugDevelopmentExpenses" id="Fact_9551753b08b4443a850a2e0b4da96da8" contextRef="c20220101to20221231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">426,225</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Medical affairs</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:MedicalAffairsExpenses" id="Fact_1732699779c143838d99de52f3b3a4fc" contextRef="c20240101to20241231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,229</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:MedicalAffairsExpenses" id="Fact_e39bfa39fe4b4948b7c943f3b22cf372" contextRef="c20230101to20231231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">19,454</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:MedicalAffairsExpenses" id="Fact_4cc06a326aae41c780e72ca285e14035" contextRef="c20220101to20221231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,948</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Manufacturing and development chemistry</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ManufacturingAndDevelopmentChemistryExpenses" id="Fact_b98900cf62d2447a947e6f7c8a16412f" contextRef="c20240101to20241231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">57,729</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ManufacturingAndDevelopmentChemistryExpenses" id="Fact_91060ec31b0c45a3a3bb04784bf24e1c" contextRef="c20230101to20231231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">65,293</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ManufacturingAndDevelopmentChemistryExpenses" id="Fact_c130410b507f41b88426c6cebaad7225" contextRef="c20220101to20221231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">76,162</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D support</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ResearchAndDevelopmentSupportExpenses" id="Fact_f55b584715244af4a03574610619f83b" contextRef="c20240101to20241231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">82,559</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consolidated net loss</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_cc6ecc60baa1460690e4dc8e8287b24f" contextRef="c20240101to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_76e328bee0ff4929ac6322c1bc189450" contextRef="c20240101to20241231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">453,897</ix:nonFraction></ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_e8cffcfe49284738bc0b22f4da3d7db2" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_1d82ce3ff9f445d99b08bd2da682d8de" contextRef="c20220101to20221231_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></ix:nonFraction></div>
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
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  </tr>


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<div><br/>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

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<div><ix:nonNumeric name="us-gaap:QuarterlyFinancialInformationTextBlock" id="Text_4be6328593df49c295c60f8f5c9d4bc0" contextRef="c20240101to20241231" escape="true" continuedAt="Text_6d783f3e932a4ec28df4358484074a3d1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">13. Fourth Quarter Financial Data (Unaudited)</div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following financial information reflects all normal recurring adjustments, which are, in the opinion of management, necessary for a
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    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31,</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
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    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss from operations</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_c3c0e5d7387e40eb92385001e70edef5" contextRef="c20241001to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">110,821</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_e656146c3d254200b1d7c79c8135fb39" contextRef="c20231001to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">6,122</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_64bf3d68a9a94552bd3463e1e35b0df2" contextRef="c20241001to20241231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">104,349</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_af25cdfae24542caac610d75303df0eb" contextRef="c20231001to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">9,263</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share (3) (4)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_cd1a45a0547d47c59adf0ba90c1e5105" contextRef="c20241001to20241231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.66</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_bdec6ddb89aa427eb5832c982172b15b" contextRef="c20231001to20231231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.06</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Diluted net loss per share (3) (5)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_a89ed465fb1d45109c8bb5281937ec8f" contextRef="c20241001to20241231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.66</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_50ffd0d9a803420490859b8fc30d4b07" contextRef="c20231001to20231231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.06</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_6d783f3e932a4ec28df4358484074a3d5" continuedAt="Text_6d783f3e932a4ec28df4358484074a3d6"><ix:continuation id="Text_a706c194770248f790db35861783f2433" continuedAt="Text_a706c194770248f790db35861783f2434">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_6d783f3e932a4ec28df4358484074a3d6" continuedAt="Text_6d783f3e932a4ec28df4358484074a3d7"><ix:continuation id="Text_a706c194770248f790db35861783f2434" continuedAt="Text_a706c194770248f790db35861783f2435">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_260ceacf638c4b6691c7c678cfe81725" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue was lower in the three months ended December 31, 2024 compared to the same period in 2023 primarily due to significant partner payments earned in the fourth quarter of 2023, including the $</span><ix:nonFraction name="us-gaap:Revenues" id="Fact_75e24768ba824a2b9a04b8c91d513855" contextRef="c20231001to20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">50</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment we earned from AstraZeneca when the FDA
              approved WAINUA for ATTRv-PN in the U.S., $</span><ix:nonFraction name="us-gaap:Revenues" id="Fact_14c3c8ccfb6f458f890a035fb5e35122" contextRef="c20231001to20231231_ProductOrServiceAxis_Ion826Member_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">36</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
              million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis. </span>In addition, WAINUA
            joint development revenue decreased in the three months ended December 31, 2024 compared to the same period in 2023 as development activities relating to ATTRv-PN wound down with the launch of WAINUA.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_6d783f3e932a4ec28df4358484074a3d7" continuedAt="Text_6d783f3e932a4ec28df4358484074a3d8"><ix:continuation id="Text_a706c194770248f790db35861783f2435" continuedAt="Text_a706c194770248f790db35861783f2436">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_6d783f3e932a4ec28df4358484074a3d8" continuedAt="Text_6d783f3e932a4ec28df4358484074a3d9"><ix:continuation id="Text_a706c194770248f790db35861783f2436" continuedAt="Text_a706c194770248f790db35861783f2437">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_94f9411e48574896ba56a419ae90ffb3" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Operating expenses were relatively consistent in the three months
            ended December 31, 2024 compared to the same period in 2023.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_6d783f3e932a4ec28df4358484074a3d9" continuedAt="Text_6d783f3e932a4ec28df4358484074a3d10"><ix:continuation id="Text_a706c194770248f790db35861783f2437" continuedAt="Text_a706c194770248f790db35861783f2438">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_6d783f3e932a4ec28df4358484074a3d10" continuedAt="Text_6d783f3e932a4ec28df4358484074a3d11"><ix:continuation id="Text_a706c194770248f790db35861783f2438" continuedAt="Text_a706c194770248f790db35861783f2439">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_bcf863dbf8484660b7f8b1e68ba84eea" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </span>compute net loss per share independently for each quarter during <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</span></ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_6d783f3e932a4ec28df4358484074a3d11" continuedAt="Text_6d783f3e932a4ec28df4358484074a3d12"><ix:continuation id="Text_a706c194770248f790db35861783f2439" continuedAt="Text_a706c194770248f790db35861783f24310">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_6d783f3e932a4ec28df4358484074a3d12" continuedAt="Text_6d783f3e932a4ec28df4358484074a3d13"><ix:continuation id="Text_a706c194770248f790db35861783f24310" continuedAt="Text_a706c194770248f790db35861783f24311">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_c0533346434a4ade8e1ac885e65ef0e6" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">As discussed in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies, </span>we compute basic net loss per share by dividing the total net loss by our weighted-average number of common shares outstanding
            during the period.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_6d783f3e932a4ec28df4358484074a3d13" continuedAt="Text_6d783f3e932a4ec28df4358484074a3d14"><ix:continuation id="Text_a706c194770248f790db35861783f24311" continuedAt="Text_a706c194770248f790db35861783f24312">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_6d783f3e932a4ec28df4358484074a3d14"><ix:continuation id="Text_a706c194770248f790db35861783f24312">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;" class="DSPFListTable">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_ccc78f604f554447aaa873d5b5a1820b" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">We incurred a net loss for the fourth quarter of 2024 and 2023. As a
            result, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation></div>


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<DOCUMENT>
<TYPE>EX-10.58
<SEQUENCE>2
<FILENAME>exhibit10-58.htm
<DESCRIPTION>EXHIBIT 10.58
<TEXT>
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  <head>
    <title></title>
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    <div>
      <div style="font-weight: bold;">
        <div style="text-align: justify; font-style: italic; font-weight: normal;">Final Execution Version</div>
      </div>
      <div style="text-align: right; font-weight: bold;"> <br>
      </div>
      <div style="text-align: right; font-weight: bold;">Exhibit 10.58</div>
      <div><br>
      </div>
      <div style="text-align: center;">Certain portions of this exhibit, marked by [***], have been excluded because they are both not material and are the type that the registrant treats as private or confidential.</div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;">AMENDMENT NO. 4</div>
      <div><br>
      </div>
      <div style="text-align: justify;">This Amendment No. 4 (the &#8220;<font style="font-weight: bold; font-style: italic;">Fourth Amendment</font>&#8221;) to the Strategic Collaboration Agreement, dated July 31, 2015, as previously amended by Amendment No. 1 dated
        October 18, 2018, Amendment No. 2 dated April 30, 2020, Amendment No. 3 dated December 17, 2020, and that certain letter agreement regarding [***] (the &#8220;[***]<font style="font-weight: bold; font-style: italic;"> Letter Agreement</font>&#8221;) dated
        August 28, 2024 (the &#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;) is made by and between</div>
      <div><br>
      </div>
      <div style="text-align: justify;">(1)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; ASTRAZENECA AB, a company incorporated in Sweden under no. 556011-7482 with its registered office at SE-151 85 S&#246;dert&#228;lje, Sweden (&#8220;<font style="font-weight: bold; font-style: italic;">AstraZeneca</font>&#8221;)


        and</div>
      <div><br>
      </div>
      <div style="text-align: justify;">(2)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; IONIS PHARMACEUTICALS, INC., a Delaware corporation, (formerly known as Isis Pharmaceuticals, Inc.) having its principal place of business at 2855 Gazelle Court, Carlsbad, California 92010 (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;),</div>
      <div><br>
      </div>
      <div style="text-align: justify;">and is made effective as of December 23, 2024 (the &#8220;<font style="font-weight: bold; font-style: italic;">Fourth Amendment Effective Date</font>).</div>
      <div><br>
      </div>
      <div style="text-align: justify; font-weight: bold;"><u>Recitals</u></div>
      <div><br>
      </div>
      <div style="text-align: justify;">WHEREAS, the Parties entered into the Agreement to establish a strategic collaboration focused on the Primary Diseases;</div>
      <div><br>
      </div>
      <div style="text-align: justify;">WHEREAS, as of the Fourth Amendment Effective Date, and in accordance with the Agreement, AstraZeneca is Developing the following: (i) a Product that comprises a Compound designed to bind to APOL1 (each, an &#8220;<font style="font-weight: bold; font-style: italic;">APOL1 Product</font>&#8221;); (ii) a Product that comprises a Compound designed to bind to PNPLA3 (each, a &#8220;<font style="font-weight: bold; font-style: italic;">PNPLA3 Product</font>&#8221;), and (iii) a Product
        that comprises a Compound designed to bind to [***] (each such Product, [***] &#8220;[***]<font style="font-weight: bold; font-style: italic;"> Product</font>&#8221; and<font style="font-weight: bold; font-style: italic;">&#160;</font>together with the APOL1
        Products and PNPLA3 Products, the &#8220;<font style="font-weight: bold; font-style: italic;">Collaboration Products</font>&#8221;);</div>
      <div><br>
      </div>
      <div style="text-align: justify;">WHEREAS, the Parties now desire to amend and restate certain financial provisions of the Agreement with respect to the Collaboration Products;</div>
      <div><br>
      </div>
      <div style="text-align: justify;">WHEREAS, in addition to the Collaboration Products, AstraZeneca seeks to develop an antisense drug discovered by Ionis targeting [***] for the treatment of pulmonary diseases; and</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">WHEREAS, Ionis now desires to grant to AstraZeneca, and AstraZeneca now desires to accept from Ionis, an exclusive license to Develop, Manufacture and Commercialize the [***] Products. </div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">1</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: justify; font-weight: bold;"><u>Agreement</u></div>
      <div><br>
      </div>
      <div style="text-align: justify;">NOW, THEREFORE, in consideration of the mutual covenants contained in this Fourth Amendment, and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties,
        intending to be legally bound, agree as follows:</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd94067de06dd4f42a26909da8e1be280">

          <tr>
            <td style="width: 18pt; vertical-align: top;">1.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-weight: bold;">Definitions</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify;">Any capitalized term not separately defined in this Fourth Amendment will have the meaning ascribed to it in the Agreement.</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za18026b4c6e44ed794070e7d6e35dcb4">

          <tr>
            <td style="width: 18pt; vertical-align: top;">2.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-weight: bold;">Modifications</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z75a37bf651e145e2a56f0ea59e0635ed">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">a.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 3.1.1</u></font><font style="font-size: 10pt;">.&#160; <u>Section 3.1.1</u> (Ionis&#8217; and AstraZeneca&#8217;s Exclusivity Covenants) is hereby amended by adding
                  the following, as new subclause (d), at the end of <u>Section 3.1.1</u> (Ionis&#8217; and AstraZeneca&#8217;s Exclusivity Covenants):</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 36pt;">&#8220;<font style="font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-style: italic;"><u>[***] After </u><u>Fourth Amendment Effective Date</u></font><font style="font-weight: bold;">.</font>&#160; The development or commercialization of an ASO that is designed to bind to [***] after the Fourth Amendment Effective Date, (1) with respect to development of an ASO that is designed to bind to [***], until [***] or [***], and
        (2) on a country-by-country basis with respect to commercialization of an ASO that is designed to bind to [***], until [***].&#8221;</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfb191c8912494131b518911628430c3f">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">b.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 3.1.3(a)(ii)</u></font><font style="font-size: 10pt;">.&#160; <u>Section 3.1.3(a)(ii)</u> is hereby deleted in its entirety and replaced with the
                  following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zcc58bae0d1c14105914d8eda880bd8bf">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">(ii)</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Any activities permitted under the Prior Agreements as such agreements are in effect on, with respect to any Collaboration Target, the date the Target is put on the High Interest Target List (or, with respect to [***], the Fourth
                Amendment Effective Date) and have been disclosed to AstraZeneca (and not as such Prior Agreements may be amended after such date); and&#8221;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9666cb87516f4af6af4fd6c94676d575">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">c.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>ARTICLE 4</u></font><font style="font-size: 10pt;">.&#160; <u>ARTICLE 4</u> (License Grants; Technology Transfer and Support) is hereby amended in accordance with
                  the below.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zafb29e78305f41ceae3ab027a0b4e3ac">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">i.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>Section 4.1.1</u> (Collaboration Target Development and Commercialization Licenses) is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" id="zf53e598fea8a42acabdc5719b80c080b" class="DSPFListTable">

            <tr style="vertical-align: top;">
              <td style="width: 54pt;">&#160;</td>
              <td style="text-align: right; vertical-align: top; width: 54pt;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">4.1.1</font></div>
              </td>
              <td style="text-align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-weight: bold;"><u>Development and Commercialization Licenses</u>.</font></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf480a5d9eddd4858ab55f4ca0572cd86">

          <tr>
            <td style="width: 108pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Collaboration Product Development and Commercialization Licenses</u>.</font><font style="font-size: 10pt;">&#160; With respect to each Collaboration Product,
                  subject to the terms and conditions of this Agreement, Ionis hereby grants AstraZeneca a worldwide, exclusive (including with regard to Ionis and its Affiliates), perpetual and irrevocable (except as otherwise expressly provided in this
                  Agreement), royalty-bearing, sublicensable (in accordance with <u>Section 4.1.2</u> below) license under the Licensed Technology to Research, Develop, Manufacture, have Manufactured (in accordance with <u>Section 4.1.2</u> below) and
                  Commercialize such Collaboration Product in the Field.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">2</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z2be2dac1e3584f8b9a3e7732f2cba6c0">

          <tr>
            <td style="width: 108pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>[***] Product Development and Commercialization Licenses</u>.</font><font style="font-size: 10pt;">&#160; As of the Fourth Amendment Effective Date, with respect to
                  each [***] Product, subject to the terms and conditions of this Agreement, Ionis hereby grants AstraZeneca a worldwide, exclusive (including with regard to Ionis and its Affiliates), perpetual and irrevocable (except as otherwise
                  expressly provided in this Agreement), royalty&#8209;bearing, sublicensable (in accordance with <u>Section 4.1.2</u> below) license under the Licensed Technology to Research, Develop, Manufacture, have Manufactured (in accordance with <u>Section


                    4.1.2</u> below) and Commercialize such [***] Product in the Field.&#8221;;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc5c558b987b540689cbc2f9d5d3afae6">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">ii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>Section 4.1.3</u> (Consequence of Natural Expiration of this Agreement) is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4af459f6c97c4c028237947c5ac433d3">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">4.1.3</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Consequence of Natural Expiration of this Agreement</u>.</font><font style="font-size: 10pt;">&#160; On a Product&#8209;by&#8209;Product basis, if this Agreement expires (<u>i.e.</u>,
                  is not terminated early) in a particular country in accordance with <u>Section 10.1</u> then, in addition to the terms set forth in <u>Section 10.3.1(c)</u>, <u>Section 10.3.1(f)</u>, <u>Section 10.3.1(g)</u> and <u>Section 10.3.1(h)</u>,
                  the applicable license under <u>Section 4.1.1</u> to the Licensed Know-How for such Product will automatically convert into a perpetual, non-exclusive, worldwide, royalty-free, fully paid-up, sublicensable license under the Licensed
                  Know-How to Manufacture, Research, Develop and Commercialize the Product that is the subject of such expiration in such country.&#8221;;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf4834c6c03f3487eab3e9b1de32a2d1e">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">iii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>Section 4.1.5</u> (License Conditions; Limitations) is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z77833d69f3544ab9ac9ad35f9f076900">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">4.1.5.</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>License Conditions; Limitations</u>.</font><font style="font-size: 10pt;">&#160; Subject to <u>Section 6.8</u> and <u>Section 6.9</u>, on a Product-by-Product
                  basis, the licenses granted under <u>Section 4.1.1</u> and the sublicense rights under <u>Section 4.1.2</u> are subject to and limited by (i) the Prior Agreements as such agreements are in effect on, with respect to the Collaboration
                  Products, the date the Collaboration Target was designated as a High Interest Target and placed on the High Interest Target List (or, with respect to [***] Products, the Fourth Amendment Effective Date) and have been disclosed to
                  AstraZeneca prior to such date (and not as such Prior Agreement may be amended thereafter), (ii) the Ionis In-License Agreements as such agreements are in effect on the date identified as Ionis In-License Agreements and added to <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 3</u> as provided in <u>Section 6.8.5</u> (and in the form disclosed to AstraZeneca prior to such date and not as such Ionis In-License Agreements may be amended thereafter
                  unless such amendment is made with AstraZeneca&#8217;s prior written consent); and (iii) the granting of, or performance of obligations under, Permitted Licenses.&#8221;;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">3</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0cb5f41694d34f42a36457bffbeed52c">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">iv.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>Section 4.2.1</u> (Assignment of Ionis Product-Specific Patents; Grant Back to Ionis) is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7a4db4e4263c4396b5dcc14ac35141fa">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">4.2.1.</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>On a Licensed Program-by-Licensed Program basis, at any time after completion of the first Phase 2 Study for the applicable Product from such Licensed Program, after discussion by the IP Managers, Ionis will assign to AstraZeneca (and
                AstraZeneca will accept from Ionis), Ionis&#8217; ownership interest in all Ionis Product-Specific Patents within the Licensed Patents that are owned by Ionis (whether solely owned or jointly owned with one or more Third Parties); <font style="font-style: italic;">provided that</font>, if either Party reasonably determines that such assignment would be likely to adversely affect the applicable Licensed Patent (including diminishing the scope, term, validity or
                enforceability of such Licensed Patent), then, [***]&#8221;; and</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z837e5e89f2164c89a6c1abc0a387c554">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">v.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>ARTICLE 4</u> (License Grants; Technology Transfer and Support) is hereby amended by inserting after <u>Section 4.8</u> (Technology Transfer) the following new <u>Sections 4.9</u>,
                  <u>4.10 </u>and <u>4.11</u>:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfe413730b4074e74aa1ec4c181e2ae54">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">4.9</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Lead [***] Compound Technology Transfer</u></font><font style="font-size: 10pt;">.&#160; With respect to the Lead [***] Compound, after the Fourth Amendment
                  Effective Date, Ionis will deliver to AstraZeneca the Licensed Know-How identified in the technology transfer plan attached hereto as <font style="font-variant: small-caps;"><u>Appendix 9</u></font>, which such Licensed Know-How
                  comprises the Licensed Know-How described in <u>Section 4.9.1</u> and <u>Section 4.9.2</u>.&#160; Within 30 days following the Fourth Amendment Effective Date or as otherwise agreed by the Parties, designated representatives of each Party
                  will meet to identify any Licensed Know-How related to the Lead [***] Compound that Ionis did not initially provide hereunder and the timeline(s) for the transfer thereof from Ionis to AstraZeneca.&#160; If any additional Licensed Know-How
                  related to the Lead [***] Compound was identified, then the Parties will amend <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 9</u> to include such Licensed-Know How and timeline(s) promptly after such meeting.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9bcb9f65aea74b5d8b7bb3b76f87e1f2">

          <tr>
            <td style="width: 108pt;">&#160;</td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.9.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Licensed Know-How &#8211; Generally</u>.</font><font style="font-size: 10pt;">&#160; Copies of Licensed Know-How (other than the Ionis Manufacturing and Analytical
                  Know-How) in the Field in Ionis&#8217; possession, for use solely in accordance with the licenses granted under <u>Section 4.1.1(b)</u> and <u>Section 4.3</u>, to AstraZeneca together with any regulatory documentation (including drafts, if
                  any) related to the Lead [***] Compound.&#160; To assist with the transfer of such Licensed Know-How, Ionis will provide [***] consulting support hours to AstraZeneca during normal business hours in furtherance of such transfer, including
                  [***].</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">4</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9c53944031ad43869062d38ce939b8a5">

          <tr>
            <td style="width: 108pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.9.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Ionis Manufacturing and Analytical Know-How</u>.</font><font style="font-size: 10pt;">&#160; Solely for use by AstraZeneca, its Affiliates or a Third Party acting
                  on AstraZeneca&#8217;s behalf to Manufacture API for [***] Products for AstraZeneca, its Affiliates or Sublicensees, in AstraZeneca&#8217;s own, or an Affiliate&#8217;s, or up to two mutually agreed Licensed CMO&#8217;s manufacturing facility, copies of the
                  Ionis Manufacturing and Analytical Know-How relating to the Lead [***] Compound in Ionis&#8217; possession, which is necessary for the exercise by AstraZeneca, its Affiliates or a Third Party of the Manufacturing rights granted under <u>Section


                    4.1.1(b)</u>.&#160; Ionis will provide [***] consulting support hours to AstraZeneca during normal business hours in furtherance of such transfer, including [***].</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4a44e891c7d34468b635ec0e75b544d5">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top; font-weight: bold;">4.10</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Technology Transfer for [***]</u></font><font style="font-size: 10pt;">.&#160; AstraZeneca may request that Ionis deliver Licensed Know-How with respect to [***]
                  pursuant to a written technology transfer plan to be mutually agreed by Ionis and AstraZeneca. Promptly following such AstraZeneca request, designated representatives of each Party will meet to identify Licensed Know-How in Ionis&#8217;
                  possession that has not previously been provided hereunder and is related to the [***] that are the subject of AstraZeneca&#8217;s request.&#160; Any such technology transfer plan for delivery of Licensed Know-How pursuant to this <u>Section 4.10</u>
                  will correspond to delivery of the Licensed Know-How as described in <u>Section 4.9.1</u> and <u>Section 4.9.2</u> but with respect to such [***].</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z634e6daf3764486abfcd375b15a19659">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top; font-weight: bold;">4.11</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Cooperation Plans</u></font><font style="font-size: 10pt;">.&#160; Either Party may propose to the other Party a program of coordinated activities between the
                  Parties to support progress of one or more of the Licensed Programs.&#160; If the other Party, at its sole discretion, determines to engage with the requesting Party in such proposed activities, then each Alliance Manager will confer with the
                  applicable representatives from its respective Party and, thereafter, the Alliance Managers will prepare and agree upon a written cooperation plan that details the activities agreed for such engagement between the Parties (each such plan,
                  a &#8220;<font style="font-weight: bold; font-style: italic;">Cooperation Plan</font>&#8221;).&#160; Each Party will use Commercially Reasonable Efforts to conduct its designated activities under such Cooperation Plan in accordance with the timelines
                  specified therein and at its own expense, unless otherwise specified in writing in such Cooperation Plan.&#8221;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3b80b6f6f28c4d4ea04f0740224cba4f">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">d.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 5.1</u></font><font style="font-size: 10pt;">.&#160; <u>Section 5.1</u> (AstraZeneca Diligence) is hereby deleted in its entirety and replaced with the
                  following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">5</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z294792a00e5b493b880577a5b2155e46">

          <tr>
            <td style="width: 36pt;">&#160;</td>
            <td style="width: 27pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">5.1</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>AstraZeneca Diligence</u>.</font><font style="font-size: 10pt;">&#160; On a Licensed Program-by-Licensed Program basis, (a) with respect to the Collaboration
                  Products, commencing on the Collaboration Program Exercise Date for the applicable Collaboration Product, and (b) with respect to the [***] Products, commencing on the Fourth Amendment Effective Date, except as expressly provided
                  otherwise in this Agreement, AstraZeneca is solely responsible for the Development, Manufacture and Commercialization of the Collaboration Products and the [***] Products, and will be solely responsible for all costs associated
                  therewith.&#160; With respect to each Licensed Program, AstraZeneca will use Commercially Reasonable Efforts (i) to Develop a Product and to seek Approval for such Product for use in humans [***], (ii) following Approval, to Commercialize such
                  Product for use in humans [***], (iii) to Develop and Commercialize a Product for use in humans worldwide (outside of [***]) to the extent consistent with the global commercialization strategy and efforts AstraZeneca would use for
                  AstraZeneca&#8217;s similar products in the same franchise, and (iv) to Develop and Commercialize each Product substantially in accordance with the applicable IPP.&#8221;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z361ef64e1bb84c66bd864d6dd9b7cdbe">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">e.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 5.1.1</u></font><font style="font-size: 10pt;">.&#160; The first sentence of <u>Section 5.1.1</u> (Specific Performance Milestone Events) is hereby deleted
                  in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 36pt;">&#8220;On a Licensed Program-by-Licensed Program basis, within [***] after the Collaboration Program Exercise Date (or, with respect to the [***] Licensed Program, [***] after the Fourth Amendment
        Effective Date), AstraZeneca will identify and provide to Ionis specific performance milestone events (&#8220;<font style="font-weight: bold; font-style: italic;">Specific Performance Milestone Events</font>&#8221;) for the first Product from such Licensed
        Program and the [***] based on the information then available to AstraZeneca and its then-current practices, and in all cases consistent with AstraZeneca&#8217;s then current internal specific performance milestone event metrics for the applicable
        AstraZeneca franchise.&#8221;</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z827d39342c8f4b90b2777479f9df0579">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">f.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 5.1.2</u></font><font style="font-size: 10pt;">.&#160; <u>Section 5.1.2</u> (Integrated Product Plans) is hereby deleted in its entirety and replaced with
                  the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 36pt;">&#8220;For each Licensed Program, AstraZeneca will prepare a global integrated Product plan or a comparable document consistent with AstraZeneca&#8217;s then current internal practices for AstraZeneca&#8217;s
        internal programs outlining key aspects of the Development and Commercialization of the Product from such Licensed Program (each plan or other such document, an &#8220;<font style="font-weight: bold; font-style: italic;">Integrated Product Plan</font>&#8221;
        or &#8220;<font style="font-weight: bold; font-style: italic;">IPP</font>&#8221;), including high level aspects of regulatory strategy and submission dates for necessary filings with applicable Regulatory Authorities to support Approval of such Product.&#160; On a
        Product-by-Product basis, AstraZeneca will prepare each IPP no later than [***] for the relevant Product, and the IPP will contain high level information consistent with AstraZeneca&#8217;s development and commercialization plans for its similar products
        at similar stages of development and commercialization in the same AstraZeneca franchise,&#160; including without limitation a status update, timelines, goals, and the criteria AstraZeneca will use to make internal decisions, but excluding information
        that AstraZeneca is required not to share even under confidentiality pursuant to restrictions imposed by any Third Party.&#160; Once AstraZeneca has prepared an IPP, AstraZeneca will update it consistent with AstraZeneca&#8217;s standard practice consistently
        applied (including if the IPP is updated and presented to an AstraZeneca internal committee) but at least Annually and will provide such updates promptly to Ionis.&#160; AstraZeneca and Ionis will meet (through the JSC or as the Parties may otherwise
        agree) on a yearly basis to discuss the draft of the IPP and AstraZeneca will consider, in good faith, any proposals and comments made by Ionis for incorporation in the IPP.&#160; AstraZeneca and Ionis will [***], to discuss the status of execution of
        the IPP.&#160; Additionally, subject to AstraZeneca&#8217;s confidentiality obligations to any Third Party, AstraZeneca will provide more frequent updates in the case of extraordinary material events (e.g., approvals, regulatory feedback, etc.) consistent
        with AstraZeneca&#8217;s standard practice consistently applied.&#160; For the avoidance of doubt, information provided by AstraZeneca to Ionis pursuant to this <u>Section 5.1.2</u> shall be treated by Ionis as AstraZeneca&#8217;s Confidential Information subject
        to the provisions in <u>ARTICLE 11</u>.&#8221;</div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">6</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z56b3d865b2bb4c76b033a27be642f7c5">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">g.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 5.3.3</u></font><font style="font-size: 10pt;">.&#160; The following sentence is hereby added as the second sentence of <u>Section 5.3.3</u> (Assistance
                  with Regulatory Filings):</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 36pt;">&#8220;After the Fourth Amendment Effective Date, upon AstraZeneca&#8217;s written request [***], Ionis will prepare the reports that, with respect to [***] Products, pertain to any Research and Development
        conducted by Ionis, as required for inclusion in the IND for such [***] Product.&#8221;</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zaf389c524a4c4351b56c6bc6ad6b5ff5">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">h.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 5.4.1</u></font><font style="font-size: 10pt;">.&#160; <u>Section 5.4.1</u> is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5d427e7e30254760adb4ee6c02284db4">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">5.4.1.</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis maintains an internal database that includes information regarding the tolerability of its drug compounds, individually and as a class, including information discovered during pre-clinical and clinical development (the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Internal ASO Safety Database</font>&#8221;).&#160; In an effort to maximize understanding of the safety profile and pharmacokinetics of Ionis compounds, AstraZeneca will cooperate in connection
                with populating the Ionis Internal ASO Safety Database, <font style="font-style: italic;">provided that </font>AstraZeneca&#8217;s obligations pursuant to this <u>Section 5.4.1</u> are subject to AstraZeneca&#8217;s compliance with Applicable Laws
                and obligations to Third Parties pursuant to binding contractual commitments entered into with respect to the conduct of any Clinical Study of any Licensed Product and, in particular, AstraZeneca will not be required to disclose any
                information in contravention of Applicable Laws or such binding contractual commitments relating to data privacy.&#160; With respect to any binding contractual commitments entered into after the Fourth Amendment Effective Date with any Third
                Party in connection with any Clinical Study of a Licensed Product, AstraZeneca will use Commercially Reasonable Efforts to ensure that such agreements include provisions permitting the transfer of safety data to Ionis in accordance with
                this <u>Section 5.4.1</u>.&#160; AstraZeneca will provide Ionis with aggregate safety reports related to Products licensed by AstraZeneca under this Agreement, including annual Development Safety Update Reports (DSURs) as soon as practicable
                following the date such information is available to AstraZeneca (but not later than [***] after AstraZeneca&#8217;s receipt of such information).&#160; In addition, with respect to Products, AstraZeneca will provide Ionis with copies of the safety
                sections of any final clinical study reports following completion of each Clinical Study. The Parties will discuss in good faith [***].&#160; Furthermore, AstraZeneca will answer any follow-up questions reasonably requested by Ionis to conduct
                analyses to keep Ionis and its partners informed regarding class generic properties of ASOs, including with respect to safety.&#160; All information disclosed by AstraZeneca to Ionis pursuant to this <u>Section 5.4.1</u> will be AstraZeneca
                Confidential Information; <font style="font-style: italic;">provided, however</font>, that so long as Ionis does not disclose the identity of a Product (or the relevant Target) or AstraZeneca&#8217;s identity, Ionis may disclose any such
                AstraZeneca Confidential Information to Regulatory Authorities and Ionis&#8217; other partners pursuant to <u>Section 5.4.2</u> below if such information is regarding class generic properties of ASOs and, with respect to Ionis&#8217; partners, such
                partners have agreed to a similar provision permitting the disclosure of their Confidential Information relating to ASOs to Ionis&#8217; partners.&#160; AstraZeneca will deliver all such information to Ionis for the Ionis Internal ASO Safety Database
                to Ionis Pharmaceuticals, Inc., 2855 Gazelle Court, Carlsbad, California 92010, Attention: Chief Medical Officer (or to such other address/contact designated in writing by Ionis).&#160; AstraZeneca will also cause its Affiliates and Sublicensees
                to comply with this <u>Section 5.4.1</u>.&#8221;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">7</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z2ee18f3c170d434e9a45891366a1fe42">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">i.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 5.5.1</u></font><font style="font-size: 10pt;">.&#160; <u>Section 5.5.1</u> (Initial Supply to AstraZeneca) is hereby amended in accordance with the below.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6971314422984e839df1e7e69926137a">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">i.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The following sentence is added to the end of <u>Section 5.5.1(a)</u>:</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 54pt;">&#8220;In support of AstraZeneca&#8217;s Development of [***] Products, Ionis will manufacture and supply [***] of API for a [***] Product.&#8221;; and</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1998f0d4dff5442199974728451f570a">

          <tr>
            <td style="width: 36pt;">&#160;</td>
            <td style="width: 18pt; vertical-align: top;">ii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>Section 5.5.1(d)</u> is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0c4952c19de943c0a96ab9d39732b4a6">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 45pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">(d)</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>After AstraZeneca&#8217;s exercise of its Collaboration Program License Right for the applicable Collaboration Product (or, with respect to the [***] Licensed Program, after the Fourth Amendment Effective Date), in addition to the supply set
                forth in this <u>Section 5.5</u>, Ionis will sell to AstraZeneca, if AstraZeneca desires, any other inventory of API and finished drug Product in Ionis&#8217; possession at [***].&#8221;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zae93e08702264695911102388d49a636">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">j.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 6.1</u></font><font style="font-size: 10pt;">.&#160; <u>Section 6.1</u> (Up-Front Fee) is hereby amended to include the following at the end of this
                  section:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 36pt;">&#8220;In addition, within [***] following the Fourth Amendment Effective Date, AstraZeneca will pay Ionis an up&#8209;front fee of $25,000,000 in consideration for the exclusive license granted under <u>Section


          4.1.1</u> to AstraZeneca for [***] Products.&#8221;</div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">8</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd71b385657cf4dd7bfba0d838573d745">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">k.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 6.4</u></font><font style="font-size: 10pt;">.&#160; The Parties hereby agree that, notwithstanding the provisions of <u>Section 6.4</u> (Milestone
                  Payments for Achievement of Milestone Events by a Product) of the Agreement, solely with respect to the Licensed Programs for the Fourth Amendment Products, <font style="font-variant: small-caps;"><u>Table</u></font><u> 1</u> is hereby
                  amended to read as follows:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="z08122862343941db9f6b9d957c63fa02">

            <tr>
              <td rowspan="1" colspan="5" style="width: 100%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;"><font style="font-variant: small-caps;"><u>Table</u></font><u> 1</u></div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">Product </div>
                <div style="text-align: center; font-weight: bold;">Milestone </div>
                <div style="text-align: center; font-weight: bold;">Event</div>
              </td>
              <td style="width: 20%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">PNPLA3 </div>
                <div style="text-align: center; font-weight: bold;">Product </div>
                <div style="text-align: center; font-weight: bold;">Milestone </div>
                <div style="text-align: center; font-weight: bold;">Event Payment</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">APOL1 </div>
                <div style="text-align: center; font-weight: bold;">Product </div>
                <div style="text-align: center; font-weight: bold;">Milestone </div>
                <div style="text-align: center; font-weight: bold;">Event Payment</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]<font style="font-weight: bold;"> Product </font></div>
                <div style="text-align: center;"><font style="font-weight: bold;">Milestone </font></div>
                <div style="text-align: center;"><font style="font-weight: bold;">Event Payment*</font></div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]<font style="font-weight: bold;"> Product </font></div>
                <div style="text-align: center;"><font style="font-weight: bold;">Milestone </font></div>
                <div style="text-align: center;"><font style="font-weight: bold;">Event Payment</font></div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
              <td style="width: 20%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]</div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">*With respect to the [***] Licensed Program, the Parties hereby agree that <u>Table 1a</u> (Development Milestones) of the [***] Letter Agreement is deleted in its entirety and replaced with new <font style="font-variant: small-caps;"><u>Table 1a</u></font> ([***] Licensed Program Development Milestones) set forth in <font style="font-variant: small-caps;"><u>Schedule 6.4</u></font>, attached to the Fourth Amendment.</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7f9d4382ac00483589cce5edd24cfd7f">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">l.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 6.7.1</u></font><font style="font-size: 10pt;">.&#160; The Parties hereby agree that, notwithstanding the provisions of <u>Section 6.7.1</u> (AstraZeneca
                  Full Royalty) of the Agreement:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb4db7cc0eaa64d48966c3b3062fd73b6">

          <tr>
            <td style="width: 36pt;">&#160;</td>
            <td style="width: 18pt; vertical-align: top;">i.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Solely with respect to the Licensed Program for PNPLA3 Products, <font style="font-variant: small-caps;"><u>Table</u></font><u> 2</u> is hereby amended to read as follows:</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="z1ff37fb03a0b4e76ac6a14de2e8057b8">

          <tr>
            <td colspan="4" rowspan="1" style="width: 12.46%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Table</u></font><font style="font-size: 10pt;"><u> 2</u></font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Royalty Tier</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-weight: bold;">Annual Worldwide Net Sales of Products </div>
              <div style="font-weight: bold;">from a Licensed Program</div>
              <div style="font-weight: bold;">(Applicable only to PNPLA3 Products)</div>
            </td>
            <td style="width: 33.34%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Royalty Rate</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">1</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div>For the portion of Annual Worldwide Net Sales &lt; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">2</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>For the portion of Annual Worldwide Net Sales &#8805; $[***] but &lt; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">3</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div>For the portion of Annual Worldwide Net Sales &#8805; $[***] but &lt; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">4</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>For the portion of Annual Worldwide Net Sales &#8805; $[***] but &lt; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">5</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div>For the portion of Annual Worldwide Net Sales &#8805; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">9</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9d9f117cd36b46c5aadd36a2350be89e">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">ii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Solely with respect to the Licensed Program for APOL1 Products, <font style="font-variant: small-caps;"><u>Table</u></font><u> 2</u> is hereby amended to read as follows:</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="z61ccbd8c3a4c40bc8e10f3d3ee9514bc">

          <tr>
            <td colspan="4" rowspan="1" style="width: 12.46%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Table</u></font><font style="font-size: 10pt;"><u> 2</u></font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-weight: bold;">Royalty</div>
              <div style="font-weight: bold;"> Tier</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-weight: bold;">Annual Worldwide Net Sales of Products </div>
              <div style="font-weight: bold;">from a Licensed Program</div>
              <div style="font-weight: bold;">(Applicable only to APOL1 Products)</div>
            </td>
            <td style="width: 33.34%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Royalty Rate</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">1</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div>For the portion of Annual Worldwide Net Sales &lt; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">2</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>For the portion of Annual Worldwide Net Sales &#8805; $[***] but &lt; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">3</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div>For the portion of Annual Worldwide Net Sales &#8805; $[***] but &lt; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">4</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>For the portion of Annual Worldwide Net Sales &#8805; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb6b5eefefc5b459a8020a23a758fea9b">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">iii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Solely with respect to the Licensed Program for [***] Products, <font style="font-variant: small-caps;"><u>Table</u></font><u> 2</u> is hereby amended to read as follows:</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="z40a45d3b5da3426895efb4e1a7477157">

          <tr>
            <td colspan="4" rowspan="1" style="width: 12.46%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Table</u></font><font style="font-size: 10pt;"><u> 2</u></font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-weight: bold;">Royalty</div>
              <div style="font-weight: bold;"> Tier</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-weight: bold;">Annual Worldwide Net Sales of Products </div>
              <div style="font-weight: bold;">from a Licensed Program</div>
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">(Applicable only to </font><font style="font-size: 10pt;">[***]<font style="font-weight: bold;"> Products)</font></font></div>
            </td>
            <td style="width: 33.34%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Royalty Rate**</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">1</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: justify;">For the portion of Annual Worldwide Net Sales &lt; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">2</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify;">For the portion of Annual Worldwide Net Sales &#8805; $[***] but &lt; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>
          <tr>
            <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">3</div>
            </td>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
            <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: justify;">For the portion of Annual Worldwide Net Sales &#8805; $[***]</div>
            </td>
            <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]%</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify;">**With respect to the Licensed Program for [***] Products, the Parties hereby agree that <u>Table 3a</u> (Royalties) of the [***] Letter Agreement is deleted in its entirety and replaced with new <font style="font-variant: small-caps;"><u>Table</u></font><u> 3a</u> ([***] Licensed Program Royalties) set forth in <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 6.7.1</u>, attached to the Fourth Amendment.</div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">10</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z740c0048b9af43709c3a15f39adf891b">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">iv.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Solely with respect to the [***] Licensed Program, <font style="font-variant: small-caps;"><u>Table</u></font><u> 2</u> is hereby amended to read as follows:</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="z2a9c062c330645f7a1c293051d1063e4">

            <tr>
              <td colspan="4" rowspan="1" style="width: 12.46%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;"><font style="font-variant: small-caps;"><u>Table</u></font><u> 2</u></div>
              </td>
            </tr>
            <tr>
              <td style="width: 12.46%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="font-weight: bold;">Royalty</div>
                <div style="font-weight: bold;"> Tier</div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="font-weight: bold;">Annual Worldwide Net Sales of Products </div>
                <div style="font-weight: bold;">from a Licensed Program</div>
                <div><font style="font-weight: bold;">(Applicable only to </font>[***]<font style="font-weight: bold;"> Products)</font></div>
              </td>
              <td style="width: 33.34%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">Royalty Rate</div>
              </td>
            </tr>
            <tr>
              <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">1</div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">For the portion of Annual Worldwide Net Sales &lt; $[***]</div>
              </td>
              <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">2</div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">For the portion of Annual Worldwide Net Sales &#8805; $[***] but &lt; $[***]</div>
              </td>
              <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">3</div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">For the portion of Annual Worldwide Net Sales &#8805; $[***] but &lt; $[***]</div>
              </td>
              <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">4</div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">For the portion of Annual Worldwide Net Sales &#8805; $[***] but &lt; $[***]</div>
              </td>
              <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">5</div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">For the portion of Annual Worldwide Net Sales &#8805; $[***] but &lt; $[***]</div>
              </td>
              <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 12.46%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">6</div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 54.21%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">For the portion of Annual Worldwide Net Sales &#8805; $[***]</div>
              </td>
              <td style="width: 33.34%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="63953c6150e0488ca6ed24be2c105a4c" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"></td>
            <td style="width: 18pt; vertical-align: top;">m.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>
                <div>
                  <div>
                    <div><font style="font-weight: bold;"><u>Section 6.8.2</u></font>. <u>Section 6.8.2</u> (New In-Licensed Additional Product-Specific Patents) is hereby amended in accordance with the below.</div>
                  </div>
                </div>
              </div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z63abd4d9bc86410ab84888bc72a86c17">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">i.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>&#8220;Product&#8221; in <u>Section 6.8.2(b)(1)</u> is hereby replaced with &#8220;Collaboration Product.&#8221;; and</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zee313a5675bf4696918b9595473549b8">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">ii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The following subsection is inserted after <u>Section 6.8.2(b)</u> (After Exercise of Collaboration Program License Right) as new <u>Section 6.8.2(c)</u>:</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 18pt; margin-left: 36pt;">&#8220;<font style="font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>With Respect to the [***] Product</u>.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 108pt;"><font style="font-weight: bold;">(1)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;With respect to [***] Products, following the Fourth Amendment Effective Date, AstraZeneca or Ionis, as the case may be, will promptly provide
        the other Party written notice of any additional Third Party Patent Rights necessary to practice an Ionis Product-Specific Patent to Develop or Commercialize a [***] Product (&#8220;<font style="font-weight: bold; font-style: italic;">Additional [***]
          Product-Specific Patents</font>) it believes it has identified and AstraZeneca will have the first right, but not the obligation, to negotiate with, and obtain a license from the Third Party Controlling such Additional [***] Product-Specific
        Patent.&#160; If AstraZeneca obtains any such Additional [***] Product-Specific Patents, then any and all Third Party Obligations arising under such Third Party agreement will be paid by [***] as [***].</div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">11</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: justify; margin-left: 108pt;"><font style="font-weight: bold;">(2)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If, however, AstraZeneca elects not to obtain such a license to such Additional [***] Product-Specific Patents, AstraZeneca will so notify
        Ionis, and Ionis may obtain such a license to such Additional [***] Product-Specific Patents and will include such Additional [***] Product-Specific Patent in the license granted to AstraZeneca under <u>Section 4.1.1</u> [***].&#160; On [***], such
        in-license agreement shall be an Ionis In-License Agreement and <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 3</u> shall be updated accordingly.&#8221;</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z99d6a6c3867741f9bc4e866384f63510">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">n.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 6.14</u></font><font style="font-size: 10pt;">.&#160; <u>Section 6.14</u> (Commercial Milestones for [***] Products) is hereby deleted in its entirety and
                  replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 18pt; margin-left: 18pt;">&#8220;<font style="font-weight: bold;">6.14</font>&#160;&#160;&#160;&#160; <u></u><font style="font-weight: bold;"><u>Commercial Milestones</u>.</font>&#160; In partial consideration for the rights and
        licenses granted to AstraZeneca hereunder, in accordance with <u>Section 6.5.5</u>, on a Fourth Amendment Product-by-Fourth Amendment Product and Calendar Year-by-Calendar Year basis, when the aggregate of all Net Sales of the applicable Fourth
        Amendment Product made by AstraZeneca or any of its Affiliates or Sublicensees in such Calendar Year exceeds the threshold (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Annual Net Sales Milestone Threshold</font>)<font style="font-weight: bold; font-style: italic;">&#160;</font>set forth in the left-hand column of <font style="font-variant: small-caps;"><u>Table</u></font><u> 3</u>, AstraZeneca will pay to Ionis a milestone payment (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Annual Net Sales-Based Milestone Payment</font>&#8221;)<font style="font-weight: bold; font-style: italic;">&#160;</font>in the corresponding amount set forth in the applicable column of <font style="font-variant: small-caps;"><u>Table</u></font><u> 3</u>:</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="z8489c25a068348a6b76a4926483769bb">

          <tr>
            <td colspan="5" style="width: 100%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Table</u></font><font style="font-size: 10pt;"><u> 3</u></font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 20.08%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;"><u>Annual Net </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Sales Milestone </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Threshold</u></div>
            </td>
            <td style="width: 20.05%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;"><u>Annual Net </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Sales-Based </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Milestone </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Payment for </u></div>
              <div style="text-align: center; font-weight: bold;"><u>PNPLA3 </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Products</u></div>
            </td>
            <td style="width: 19.11%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;"><u>Annual Net </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Sales-Based</u></div>
              <div style="text-align: center; font-weight: bold;"><u> Milestone </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Payment for<br>
                </u></div>
              <div style="text-align: center; font-weight: bold;"><u>&#160;APOL1 </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Products</u></div>
            </td>
            <td style="width: 21.91%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;"><u>Annual Net </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Sales-Based </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Milestone </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Payment for</u></div>
              <div style="text-align: center; font-weight: bold;"><u> [***] </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Products***</u></div>
            </td>
            <td style="width: 18.84%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;"><u>Annual Net</u></div>
              <div style="text-align: center; font-weight: bold;"><u> Sales-Based </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Milestone </u></div>
              <div style="text-align: center; font-weight: bold;"><u>Payment for</u></div>
              <div style="text-align: center; font-weight: bold;"><u> [***] Products</u></div>
            </td>
          </tr>
          <tr>
            <td style="width: 20.08%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 20.05%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 19.11%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 21.91%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 18.84%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 20.08%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 20.05%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 19.11%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 21.91%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 18.84%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 20.08%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 20.05%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 19.11%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 21.91%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 18.84%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 20.08%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 20.05%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 19.11%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 21.91%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 18.84%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 20.08%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 20.05%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 19.11%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 21.91%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 18.84%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 18pt;">If, with respect to the applicable Fourth Amendment Product, in a given Calendar Year more than one of the foregoing thresholds for such Fourth Amendment Product set forth in <font style="font-variant: small-caps;"><u>Table</u></font><u> 3</u> is exceeded, AstraZeneca will pay to Ionis a separate Annual Net Sales-Based Milestone Payment with respect to each such threshold that is exceeded in such Calendar Year for such
        Fourth Amendment Product.&#160; Each milestone payment in this <u>Section 6.14</u> (Commercial Milestones) will be payable only upon the first achievement of such milestone event for such Fourth Amendment Product in a given Calendar Year and no amounts
        shall be due for subsequent or repeated achievements of such milestone for such Fourth Amendment Product in subsequent Calendar Years.&#8221;</div>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 18pt;">***With respect to the [***] Licensed Program, the Parties hereby agree that <u>Table 2a</u> (Sales Milestones) of the [***] Letter Agreement is deleted in its entirety and replaced with <font style="font-variant: small-caps;"><u>Table 2a</u></font> ([***] Licensed Program Sales Milestones) set forth in <font style="font-variant: small-caps;"><u>Schedule 6.14</u></font>, attached to the Fourth Amendment.</div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">12</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="02f6b9900336426f95e530aec6881e73" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 18pt;"></td>
                <td style="width: 18pt; vertical-align: top;">o.</td>
                <td style="width: auto; vertical-align: top; text-align: justify;"><font style="font-weight: bold;"><u>Section 7.1.2</u></font>.&#160; The heading used for <u>Section 7.1.2</u> (Collaboration Technology) is hereby deleted in its entirety and
                  replaced with the following: &#8220;<font style="font-weight: bold;"><u>Ownership Generally</u></font>.&#8221;</td>
              </tr>

          </table>
          <div> <br>
          </div>
          <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="0508834478cd4c4cb379b608ec88fa49" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 18pt;"><br>
                </td>
                <td style="width: 18pt; vertical-align: top;">p. </td>
                <td style="width: auto; vertical-align: top; text-align: justify;"><font style="font-weight: bold;"><u>Section 7.1.4</u></font>.<u>&#160;&#160; Section 7.1.4</u> (Jointly Owned Collaboration Technology) is hereby amended in accordance with the
                  following:</td>
              </tr>

          </table>
          <div> <br>
          </div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z14f712619fd844c89dd9204212b0c30e">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">i.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The heading used for <u>Section 7.1.4</u> is hereby deleted in its entirety and replaced with the following: &#8220;<font style="font-weight: bold;"><u>Joint Ownership</u></font>.&#8221;; and</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf821d85e205c425196f3d037877df2eb">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">ii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The following sentences are hereby added to the end of <u>Section 7.1.4</u>:</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 54pt;">&#8220;Other than Jointly-Owned Collaboration Technology that arose from performance of a Collaboration Plan or that arises from performance of any Cooperation Plan, the Parties do not intend that any
        Know-How be conceived, discovered, developed or otherwise made jointly by or on behalf of the Parties (or their respective Affiliates) under or in connection with this Agreement or that any jointly-owned Patent Rights or other intellectual property
        rights will arise with respect thereto (&#8220;<font style="font-weight: bold; font-style: italic;">Other Joint Technology</font>&#8221;).&#160; As such, Ionis is under no obligation to provide any support to AstraZeneca except (i) as expressly set forth in the
        technology transfer plan under <u>Section 4.9</u> (Lead [***] Compound Technology Transfer), which is attached hereto as <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 9</u>, (ii) in accordance with <u>Section 4.9.1</u>
        (Licensed Know-How &#8211; Generally) and <u>Section 4.9.2</u> (Ionis Manufacturing and Analytical Know-How), (iii) as expressly set forth in a technology transfer plan agreed under <u>Section 4.10</u> (Technology&#160; Transfer for [***]), and (iv) under
        any Cooperation Plan agreed in accordance with <u>Section 4.11</u> (Cooperation Plans).&#160; In the event that any such Other Joint Technology does arise, each Party shall promptly disclose to its own IP Manager regarding the matter.&#160; Thereafter, each
        Party&#8217;s respective IP Manager will meet to discuss the information received for coordination regarding any further actions to take with respect to such Other Joint Technology.&#8221;</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1337ed3252334c69afe0bac45784e6d2">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">q.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 7.2.2(b)</u></font><font style="font-size: 10pt;">.&#160; <u>Section 7.2.2(b)</u> (Ionis Product-Specific Patents and Jointly-Owned Collaboration Patents)
                  is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z25d123edaa33410f89ca80f6d5b0f3f9">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">(b)</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Ionis Product-Specific Patents and Jointly-Owned Collaboration Patents</u>.</font><font style="font-size: 10pt;">&#160; On an Exclusive Target-by-Exclusive Target
                  basis, following the Collaboration Program Exercise Date with respect to such Exclusive Target (or, with respect to [***], following the Fourth Amendment Effective Date) so long as the applicable license to AstraZeneca under <u>Section
                    4.1.1</u> is in effect, AstraZeneca will control and be responsible for all aspects of the Prosecution and Maintenance of the (i) Ionis Product-Specific Patents and (ii) Jointly-Owned Collaboration Patents that are not Ionis Core
                  Technology Patents or Ionis Manufacturing and Analytical Patents, in each case (i) and (ii) to the same extent Ionis had the right to control and was responsible for such Prosecution and Maintenance immediately prior to such license (or
                  such milestone payment), subject to <u>Section 7.2.3</u>.&#8221;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">13</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="4ae3c8a39ded4df6809079658d1c4dcb" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"></td>
            <td style="width: 18pt; vertical-align: top;">r. </td>
            <td style="width: auto; vertical-align: top; text-align: justify;"><font style="font-weight: bold;"><u>Section 7.2.4</u></font>.&#160;&#160; The following subsection is inserted after <u>Section 7.2.4(e)</u> (Other Matters Pertaining to Prosecution and
              Maintenance of Patents) as new <u>Section 7.2.4(f):</u></td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: justify; margin-left: 81.35pt;">&#8220;(f)&#160; If, at the Fourth Amendment Effective Date, no Ionis Product-Specific Patent has been filed claiming the specific composition of matter of the Lead [***] Compound, AstraZeneca will control
        and be responsible for the filing of the patent application claiming such specific composition of matter in accordance with <u>Section 7.2.2(b)</u>.&#160; The Parties will cooperate in good faith on the drafting of the patent application, with Ionis
        providing input as requested by AstraZeneca, to ensure efficient drafting and timely filing of such a patent application.&#8221;</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6aad82c23276434187b2bea0147cc978">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">s.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 7.5</u></font><font style="font-size: 10pt;">.&#160; <u>Section 7.5</u> (Enforcement of Patents Against Competitive Infringement) is hereby deleted in its
                  entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf9341b51b9fe4fc49e6510d871cb8f4f">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">7.5</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Enforcement of Patents Against Competitive Infringement</u></font><font style="font-size: 10pt;">.&#160; With respect to infringement, unauthorized use,
                  misappropriation or threatened infringement by a Third Party of any Product-Specific Patent by reason of the development, manufacture, use or commercialization of a product that binds to a Collaboration Target or to [***] in the Field (&#8220;<font style="font-weight: bold; font-style: italic;">Competitive Infringement</font>&#8221;), prior to the applicable Collaboration Program Exercise Date, or, with respect to [***], the Fourth Amendment Effective Date, Ionis will have the sole
                  right (with no obligation to discuss with AstraZeneca), but not the obligation, to institute, prosecute, and control a Proceeding with respect thereto.&#160; With respect to any Competitive Infringement after the Fourth Amendment Effective
                  Date, the Parties will handle such Competitive Infringement in accordance with the remainder of this <u>Section 7.5</u>.&#8221;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc7cd8b64248545a98cf74b161f6ef676">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">t.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 7.5.2</u></font><font style="font-size: 10pt;">.&#160; The first sentence of <u>Section 7.5.2</u> (Control of Competitive Infringement Proceedings) is
                  hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 36pt;">&#8220;For any Competitive Infringement with respect to a Product licensed to AstraZeneca under <u>Section 4.1.1</u> that occurs after the applicable Collaboration Program Exercise Date (or, with
        respect to [***] Products, that occurs after the Fourth Amendment Effective Date), so long as part of such Proceeding AstraZeneca also enforces any Patent Rights Controlled by AstraZeneca (including any Ionis Product-Specific Patents assigned by
        Ionis to AstraZeneca under this Agreement) being infringed that Cover such Product, then AstraZeneca will have the first right, but not the obligation, to institute, prosecute, and control a Proceeding with respect thereto by counsel of its own
        choice at its own expense, and Ionis will have the right, at its own expense, to be represented in that action by counsel of its own choice, <font style="font-style: italic;">however</font>, AstraZeneca will have the right to control such
        litigation.&#8221;</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0863ebacf8ac4d9ab5b2583d3ada87f9">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">u.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 7.9</u></font><font style="font-size: 10pt;">.&#160; <u>Section 7.9</u> (Obligation to Third Parties) is hereby deleted in its entirety and replaced with
                  the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">14</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf52249bf28de4f058e3b16ac583b0ffb">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">7.9</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Obligations to Third Parties</u>.&#160; </font><font style="font-size: 10pt;">Notwithstanding any of the foregoing, each Party&#8217;s rights and obligations with
                  respect to Licensed Technology under this <u>ARTICLE 7</u> will be subject to the Third Party rights and obligations under (i) Third Party agreements the restrictions and obligations of which AstraZeneca agreed to under <u>Section
                    1.13.2</u>, <u>Section 6.8.2(a)</u>, <u>Section 6.8.2(b)(2)</u>, and <u>Section 6.8.2(c)(2)</u>, (ii) Prior Agreements as such agreements are in effect on the date such Collaboration Target was designated a High Interest Target and
                  placed on the High Interest Target List (or, with respect to [***], the Fourth Amendment Effective Date) (and not as such Prior Agreement may be amended thereafter), and (iii) Ionis In-License Agreements as such agreements are in effect
                  on the date identified as Ionis In-License Agreements and added to <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 3</u> in accordance with <u>Section 6.8.5</u> and have been disclosed to AstraZeneca prior to such date
                  (and in the form disclosed to AstraZeneca prior to such date and not as such Ionis In-License Agreements may be amended thereafter unless such amendment is made with AstraZeneca&#8217;s prior written consent); <font style="font-style: italic;">provided,



                    however</font>, that, to the extent that Ionis has a non-transferable right to prosecute, maintain or enforce any Patent Rights licensed to AstraZeneca hereunder and this Agreement purports to grant any such rights to AstraZeneca, Ionis
                  will act in such regard with respect to such Patent Rights at AstraZeneca&#8217;s direction.&#8221;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4b859617da4f4c818f2d8de7368940a4">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">v.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 8.2</u></font><font style="font-size: 10pt;">.&#160; <u>Section 8.2</u> (Representations, Warranties and Covenants of Ionis) is hereby amended in
                  accordance with the below.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zae44796016be48109f85a1a7dd93f2ea">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">i.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>Section 8.2</u> (Representations, Warranties and Covenants of Ionis) is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1e6dd736b11d4b81832aaa3e04ca4f34">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">8.2.</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Representations, Warranties and Covenants of Ionis</u>.</font><font style="font-size: 10pt;">&#160; Ionis hereby represents and warrants to AstraZeneca, as of the
                  Effective Date (or, with respect to <u>Sections 8.2.13</u> through <u>8.2.22</u>, as of the Fourth Amendment Effective Date) that:&#8221;; and</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5d525ca1b85648d385a47c4d610dd213">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">ii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>Section 8.2</u> (Representations, Warranties and Covenants of Ionis) is hereby amended by adding the following new <u>Sections 8.2.13</u> through <u>8.2.22</u> at the end of <u>Section


                    8.2</u> (Representations, Warranties and Covenants of Ionis):</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0403f824abaa4d99af5aedfba04f4fb8">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">8.2.13.</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis is the owner, or otherwise has the right to grant all rights and licenses it purports to grant to AstraZeneca with respect to the Licensed Technology under this Agreement for each of the Lead [***] Compound and the Secondary [***]
                Compound as it exists on the Fourth Amendment Effective Date;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1e17ac5025044fd09238395a85ae6cea">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top; font-weight: bold;">8.2.14.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>to Ionis&#8217; Knowledge, all Licensed Patents with respect to each of the Lead [***] Compound and the Secondary [***] Compound have been filed and maintained properly and correctly in all material respects;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">15</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z80765aa43f8b43459fe9ea3d66dab9b8">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top; font-weight: bold;">8.2.15.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis has not previously entered into any agreement, whether written or oral, with respect to, or otherwise assigned, transferred, licensed, conveyed or otherwise encumbered its right, title or interest in or to, the Licensed Technology
                with respect to the Lead [***] Compound or the Secondary [***] Compound (including by granting any covenant not to sue with respect thereto) in such a way as to make the representation set forth in <u>Section 8.2.13</u> not true, and it
                will not enter into any such agreements or grant any such right, title or interest to any Person that is inconsistent with the rights and licenses granted to AstraZeneca under this Agreement;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zeb2f111b555c42d4a3ebfbbb66a70a26">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top; font-weight: bold;">8.2.16.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>to Ionis&#8217; Knowledge, each of the Licensed Patents with respect to the Lead [***] Compound or the Secondary [***] Compound properly identifies each and every inventor of the claims thereof as determined in accordance with the laws of the
                jurisdiction in which such Patent Right is issued or such application is pending;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z59f72593b32a4086b551e011563f9cd7">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top; font-weight: bold;">8.2.17.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis has not received any written claim alleging, and does not have Knowledge of any fact or circumstance, indicating, that any of the Licensed Patents with respect to the Lead [***] Compound or the Secondary [***] Compound are invalid
                or unenforceable;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z72f6e870a2404d4e83ca27870b738e9b">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top; font-weight: bold;">8.2.18.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis has not received any written claim alleging and, except as set forth in <font style="font-variant: small-caps;">Schedule </font>8.2.18, attached to the Fourth Amendment, does not have Knowledge of any fact or circumstance
                indicating that the Lead [***] Compound or the Secondary [***] Compound infringes any intellectual property rights of a Third Party;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z78a413e25b54476f8416176de97e0a7c">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top; font-weight: bold;">8.2.19.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>to Ionis&#8217; Knowledge, in respect of the pending United States patent applications included in the Licensed Patents with respect to the Lead [***] Compound or the Secondary [***] Compound, Ionis has submitted all material prior art of
                which it is aware in accordance with the requirements of the United States Patent and Trademark Office;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zad6927195cd74387b2e88dfc52eb7ee7">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top; font-weight: bold;">8.2.20.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>to Ionis&#8217; Knowledge, (i) neither Ionis nor its Affiliates owns or Controls any Patent Rights or Know How covering formulation or delivery technology as of the Fourth Amendment Effective Date and (ii) there are no additional licenses
                (beyond those granted to AstraZeneca under <u>Section 4.1.1</u>) under any intellectual property owned or Controlled by Ionis or its Affiliates as of the Fourth Amendment Effective Date, in each case (i) and (ii) that would be necessary or
                useful in order for AstraZeneca to further Develop, Manufacture or Commercialize a Product comprising the Lead [***] Compound or the Secondary [***] Compound;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">16</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z117d7df3e90d4daf990d79aee1b23b8f">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top; font-weight: bold;">8.2.21.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt;"><u> 7</u> (Prior Agreements) includes a complete and accurate list of all agreements between Ionis and
                  Third Parties relevant to [***] Compounds that create material Third Party Obligations that affect the rights granted by Ionis to AstraZeneca with respect to [***] Compounds.&#160; Such Prior Agreements have not been materially amended or
                  extended since first being placed in the Ionis data room to which AstraZeneca was given access during the negotiation of the Fourth Amendment and subject to redactions represent a true and complete and accurate copy thereof, and any such
                  redactions are of information not necessary to disclose to understand the implications of such Prior Agreements to this Agreement; and</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3e2279630c274a13a3454636b52d77f1">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 54pt; vertical-align: top; font-weight: bold;">8.2.22.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis has not conducted any clinical studies with any [***] Product and has conducted, and has required its contractors and consultants (if any) to conduct, any and all preclinical studies related to the [***] Products as required by
                Applicable Law, in each case as applicable when such activities were conducted and under the laws and regulations of the country and the state and local government wherein such activities were conducted.&#8221;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1bfc91ec51d440adaba459c477186db2">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">w.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 10.2.1(a)</u></font><font style="font-size: 10pt;">.&#160; <u>Section 10.2.1(a)</u> (Termination for Convenience or with respect to [***]) is hereby
                  deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb12440d55d82415995aa3f894c1d8ee3">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">(a)</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Termination for Convenience</u>.</font><font style="font-size: 10pt;">&#160; At any time following payment by AstraZeneca of all upfront fees under <u>Section 6.1</u>,
                  subject to <u>Section 10.3.1</u> below, AstraZeneca will be entitled to terminate this Agreement in its entirety or in part on a Licensed Program-by-Licensed Program basis for convenience by providing 90 days prior written notice to
                  Ionis of such termination.&#8221;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdab341a197624223a36b29c54eae0e12">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">x.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 10.2.3(b)</u></font><font style="font-size: 10pt;">.&#160; The last sentence of <u>Section 10.2.3(b)</u> is hereby deleted in its entirety and replaced
                  with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 36pt;">&#8220;Following such a meeting, if AstraZeneca fails to use Commercially Reasonable Efforts as contemplated in <u>ARTICLE 1</u> or <u>Section 5.1</u>, and such failure constitutes a material breach of
        this Agreement, then, subject to <u>Section 10.2.4</u> below, Ionis will have the right, at its sole discretion, to terminate this Agreement in part on a Licensed Program-by-Licensed Program basis.&#8221;</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8d0450c8228b45e59935a2f43efe8f73">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">y.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 10.2.5</u></font><font style="font-size: 10pt;">.&#160; <u>Section 10.2.5</u> (Termination of a Licensed Program) is hereby deleted in its entirety and
                  replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc02274d045df4ad29a6bf2cbf75bb1be">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">10.2.5</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Termination of a Licensed Program</u>.&#160; </font><font style="font-size: 10pt;">From and after the Fourth Amendment Effective Date, neither Party will be
                  entitled to terminate a Licensed Program pursuant to <u>Sections 10.2.2</u> or <u>10.2.3</u> unless the material breach or failure to use Commercially Reasonable Efforts is with respect to such Licensed Program and any such breach or
                  failure will be determined on a Licensed Program-by-Licensed Program basis.&#8221;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">17</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z08e835049cae44af842990b7a12cfc82">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">z.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 10.3.1</u></font><font style="font-size: 10pt;">.&#160; <u>Section 10.3.1</u> (Consequence of Termination of this Agreement) is hereby deleted in its
                  entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z624d1e9a8f34429c906bbe2da29a034b">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">10.3.1.</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Consequence of Termination of this Agreement</u>.</font><font style="font-size: 10pt;"> If this Agreement is terminated by a Party in accordance with <u>Section


                    10.2</u>, in its entirety or on a Licensed Program-by-Licensed Program basis at any time and for any reason, the following terms will apply to any such termination, but only to the extent of any such termination (<u>i.e.</u>, with
                  respect to a terminated Licensed Program (the &#8220;<font style="font-weight: bold; font-style: italic;">Terminated Program</font>&#8221; and its Target, the &#8220;<font style="font-weight: bold; font-style: italic;">Terminated Target</font>&#8221; and the
                  Products under such Terminated Program at the termination Date, the &#8220;<font style="font-weight: bold; font-style: italic;">Discontinued Products</font>&#8221;), or in its entirety):&#8221;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z60eea2d97f8c4e46b836d30b4cc07f62">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">aa.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 10.3.1(f)</u></font><font style="font-size: 10pt;">.&#160; <u>Section 10.3.1(f)</u> (Return of Information and Materials) is hereby deleted in its entirety
                  and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z01219ebaecd34eca96480eaa00abb427">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">(f)</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Return of Information and Materials</u>.</font><font style="font-size: 10pt;">&#160; The Parties will [***] any and all data, files, records and other materials
                  containing or comprising the other Party&#8217;s Confidential Information to which the Party then in possession of such Confidential Information does not retain rights under the surviving provisions of this Agreement.&#160; The Parties agree that
                  each Party will be permitted to retain one copy of any such data, files, records, and other materials for archival and legal compliance purposes, as well as any additional copies of, or any computer records or files containing, the other
                  Party&#8217;s Confidential Information that have been created solely by automatic archiving and back-up procedures (to the extent created and retained in a manner consistent with the retaining Party&#8217;s standard archiving and back-up procedures,
                  but not for any other use or purpose).&#160; All Confidential Information will continue to be subject to the terms of this Agreement for the period set forth in <u>Section 11.1</u>.&#8221;</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1de773f73fe64ea2a36f6f26ea77f44a">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">bb.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 10.3.2</u></font><font style="font-size: 10pt;">.&#160; <u>Section 10.3.2</u> (Ionis: Special Consequences of Certain Terminations) is hereby amended in
                  accordance with the below:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3df3217a76264a0cb377194cc2f7dda1">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">i.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>Section 10.3.2(a)(1)</u> is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 36pt;">&#8220;<font style="font-weight: bold;">(1)</font> a sublicensable, worldwide, exclusive license or sublicense, as the case may be, under all AstraZeneca Technology (excluding AstraZeneca Background
        Intellectual Property) Controlled by AstraZeneca as of the date of such reversion that Covers the Discontinued Product as Developed or Commercialized by AstraZeneca or its Affiliates as at such date; <font style="font-style: italic;">provided that</font>
        (i) [***] and (ii) upon Ionis&#8217; written request, AstraZeneca will [***].&#160; Ionis will confirm to AstraZeneca in any notification under <u>Section 10.3.2(a)(1)(i)</u> that, on or prior to [***].&#8221;;</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4e2a2871ced44435b5fdbe5dd8faec92">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">ii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>Section 10.3.2(c)</u> is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z75bf2786794f41c88d2d83a1ec099785">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">(c)</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>In accordance with [***] pursuant to <u>Section 10.3.1(f)</u>, AstraZeneca will transfer to Ionis for use with respect to the Development and Commercialization of the Discontinued Product, any Know-How, data, results, regulatory
                information, qualitative market research, health economic study information, material communications with payors, filings, and files in the possession of AstraZeneca, or copies thereof, as of the date of such termination or reversion that
                relate solely to such Discontinued Product;&#8221;;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">18</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z58f7639e48fd46e3938ac6d3231869cc">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">iii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>Section 10.3.2(g)</u> is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z53a7201fd85b4143b2731b03baeba647">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">(g)</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>If Ionis or any of its Affiliates or Sublicensees Commercializes a Discontinued Product for which AstraZeneca has paid Ionis the license fee under <u>Section 6.2</u> (or the up-front fee for [***] Products under <u>Section 6.1</u>) for
                a Product, then in each such case, following the First Commercial Sale of such Discontinued Product by Ionis or its Affiliates or Sublicensees, Ionis will pay AstraZeneca a royalty of [***]% of Annual worldwide Net Sales of such
                Discontinued Product until [***];&#8221;; and</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9ddcbfff603b477c813f70641932ffa6">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">iv.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;"><u>Section 10.3.2(j)</u> is hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc726d0f3d57e42309987cedd05933d7b">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">&#8220;<font style="font-weight: bold;">(j)</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>for clarity, the licenses granted by AstraZeneca pursuant to this <u>Section 10.3.2</u> do not include any intellectual property rights relating to (i) compounds or other active ingredients either alone or in combination other than the
                Compound contained in the Discontinued Product or (ii) the Exploitation of such other compound or active ingredient (either alone or in combination) or (iii) any formulation technology, delivery technology, device technology, manufacturing
                technology or other platform technology that is not necessary or used with the Discontinued Product as of the effective date of such termination to Exploit the Discontinued Product.&#160; With respect to a Discontinued Product that contains a
                [***] Compound for [***] solely for manufacture and supply of the Discontinued Product for Ionis and under industry standard confidentiality provisions reasonably acceptable to AstraZeneca.&#8221;</div>
            </td>
          </tr>

      </table>
      <div style="text-align: justify;"><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9c808bd9c98c40f7b522ed98103d6dab">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">cc.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Section 12.7</u></font><font style="font-size: 10pt;">.&#160; The contact information for each of Ionis and AstraZeneca under <u>Section 12.7</u> (Notices) is
                  hereby deleted in its entirety and replaced with the following:</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zcf784db698d34275a32dfa6f9d7fa0ec">

          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify; margin-left: 36pt;">&#8220;If to Ionis, addressed to:</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">Ionis Pharmaceuticals, Inc.</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="margin-left: 36pt;">&#160;</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">2855 Gazelle Court</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="margin-left: 36pt;">&#160;</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">Carlsbad, CA 92010</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="margin-left: 36pt;">&#160;</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">Attention: Chief Business Officer</div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 50%; vertical-align: top;">&#160;</td>
            <td rowspan="1" style="width: 50%; vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify; margin-left: 36pt;">With a copy to</div>
            </td>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify; margin-left: 36pt;">(which copy will not constitute notice):</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="margin-left: 36pt;">&#160;</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">Attention: General Counsel</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">19</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zfe96c61b774f4915a6eb100a27f44eb7">

          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify; margin-left: 36pt;">If to AstraZeneca, addressed to:</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">AstraZeneca AB</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="margin-left: 36pt;">&#160;</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">SE-431 83 M&#246;lndal</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="margin-left: 36pt;">&#160;</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">Sweden</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="margin-left: 36pt;">&#160;</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">Attention: VP, Global Head of the</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="margin-left: 36pt;">&#160;</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">Business Development and Licensing,</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="margin-left: 36pt;">&#160;</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">BioPharmaceuticals R&amp;D</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="margin-left: 36pt;">&#160;</div>
            </td>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify; margin-left: 36pt;">With a copy to</div>
            </td>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify; margin-left: 36pt;">(which copy will not constitute notice):</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">Attention: Deputy General Counsel,</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">Corporate Legal&#8221;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z718d3d8bc72344fd92072858709aba9a">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">dd.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt; font-weight: bold;"><u> 1</u></font><font style="font-size: 10pt;">.&#160; <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 1</u> (Definitions) is hereby amended as set forth in <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 1A</u> (Definitions), attached hereto.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb49a55c058a945c49058e96645910253">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">ee.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt; font-weight: bold;"><u> 4</u></font><font style="font-size: 10pt;">.&#160; <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 4</u> (Ionis Core Technology Patents) is hereby amended to include the Ionis Core Technology Patents with respect to the Lead [***] Compound and the Secondary [***] Compound,
                  which are identified in <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 4A</u> attached hereto.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z85f8931056544d7ebc5f2e4a76a94185">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">ff.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt; font-weight: bold;"><u> 5</u></font><font style="font-size: 10pt;">.&#160; <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 5</u> (Ionis Manufacturing and Analytical Patents) is hereby amended to include the Ionis Manufacturing and Analytical Patents with respect to the Lead [***] Compound and the
                  Secondary [***] Compound, which are identified in <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 5A</u> attached hereto.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z17e0603666e24ee5b3854ea47a01622e">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">gg.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt; font-weight: bold;"><u> 6</u></font><font style="font-size: 10pt;">.&#160; <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 6</u> (Ionis Product-Specific Patents) is hereby amended to include the Ionis Product-Specific Patents with respect to the [***] Products, which are identified in <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 6A</u> attached hereto.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z89e7cfc187e64a2a8a00061fbce7fcc6">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">hh.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt; font-weight: bold;"><u> 7</u></font><font style="font-size: 10pt;">.&#160; <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 7</u> (Prior Agreements) is hereby amended to include the agreements identified in <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 7A</u> (Prior Agreements),
                  attached hereto, in appropriate alphabetical order.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd84248321d774dcbbcfd4767d828c244">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">ii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;"><u>Appendices</u></font><font style="font-size: 10pt; font-weight: bold;"><u> 8A and 8B</u></font><font style="font-size: 10pt;">.&#160; The
                  Agreement is hereby amended to include new <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 8A</u> (Lead [***] Compound) and <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 8B</u> (Secondary [***]
                  Compound), attached hereto, at the end of the appendices attached to the Agreement.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z2d703f30f06046b3a1d485b14f269a11">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">jj.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt; font-weight: bold;"><u> 9</u></font><font style="font-size: 10pt;">.&#160; The Agreement
                  is hereby amended to include new <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 9</u> (Lead [***] Compound Technology Transfer Plan), attached hereto, at the end of the appendices attached to the Agreement.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zedf8063561da41029c6bd9325226f6b6">

          <tr>
            <td style="width: 18pt; vertical-align: top;">3.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-weight: bold;"><u>Fourth Amendment Effective Date</u></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify;">This Fourth Amendment will become effective on the Fourth Amendment Effective Date.</div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">20</font></div>
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          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5ef7e1d7344a4fe4a29c121c5ec40c3e">

          <tr>
            <td style="width: 18pt; vertical-align: top;">4.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-weight: bold;"><u>Entire Agreement</u></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify;">This Fourth Amendment (including all appendices attached hereto), together with the Agreement, constitutes the entire agreement between the Parties with respect to the subject matter of the Agreement.&#160; The Agreement
        together with this Fourth Amendment supersedes all prior agreements, whether written or oral, with respect to the subject matter of the Agreement, as amended.&#160; Each Party confirms that it is not relying on any representations, warranties, or
        covenants of the other Party except as specifically set out in the Agreement, as amended.&#160; Nothing in this Fourth Amendment is intended to limit or exclude any liability or fraud.&#160; The Parties hereby agree that subject to the modifications
        specifically stated in this Fourth Amendment, all other terms and conditions of the Agreement shall remain in full force and effect.</div>
      <div><br>
      </div>
      <div style="text-align: center;">[<font style="font-style: italic;">Remainder of page intentionally blank</font>. <font style="font-style: italic;"> Signatures follow</font>.]</div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">21</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: justify; font-weight: bold;"><u>Execution</u></div>
      <div><br>
      </div>
      <div style="text-align: justify;">THIS FOURTH AMENDMENT IS EXECUTED by the authorized representatives of the Parties as of the date first written above.</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z238c159c01794a19b3353494ca7650fc">

          <tr>
            <td colspan="2" style="vertical-align: top;">
              <div style="text-align: justify; font-weight: bold;">ASTRAZENECA AB (publ.)</div>
            </td>
            <td colspan="1" style="width: 6%; vertical-align: top;">&#160;</td>
            <td colspan="2" style="vertical-align: top;">
              <div style="text-align: justify; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
            </td>
          </tr>
          <tr>
            <td colspan="2" style="vertical-align: top;">&#160;</td>
            <td colspan="1" style="width: 6%; vertical-align: top;">&#160;</td>
            <td colspan="2" style="vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3%; vertical-align: top;">
              <div style="text-align: justify;">By:</div>
            </td>
            <td style="width: 44%; vertical-align: top; border-bottom: 2px solid black;">
              <div style="text-align: justify; font-size: 12pt;"><font style="font-size: 10pt; font-style: italic;">/s/</font><font style="font-size: 10pt;">&#160;</font><font style="font-size: 10pt; font-style: italic;">Ulrika Lilja</font></div>
            </td>
            <td colspan="1" style="width: 6%; vertical-align: top;">&#160;</td>
            <td style="width: 3%; vertical-align: top;">
              <div style="text-align: justify;">By:</div>
            </td>
            <td style="width: 44%; vertical-align: top; border-bottom: 2px solid black;">
              <div style="text-align: justify; font-style: italic;">/s/ Brett Monia</div>
            </td>
          </tr>
          <tr>
            <td colspan="2" style="vertical-align: top;">&#160;</td>
            <td colspan="1" style="width: 6%; vertical-align: top;">&#160;</td>
            <td colspan="2" style="vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td colspan="2" style="vertical-align: top;">
              <div style="text-align: justify;">Name: Ulrika Lilja</div>
            </td>
            <td colspan="1" style="width: 6%; vertical-align: top;">&#160;</td>
            <td colspan="2" style="vertical-align: top;">
              <div style="text-align: justify;">Name: Brett Monia</div>
            </td>
          </tr>
          <tr>
            <td colspan="2" style="vertical-align: top;">
              <div style="text-align: justify;">Title: Authorised Signatory</div>
            </td>
            <td colspan="1" style="width: 6%; vertical-align: top;">&#160;</td>
            <td colspan="2" style="vertical-align: top;">
              <div style="text-align: justify;">Title: CEO</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">22</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt;"><u> 1A</u></font></div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;">Definitions</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Additional [***] Product-Specific Patents</font>&#8221; has the meaning set forth in <u>Section 6.8.2(c)(1)</u>.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Annual Net Sales Milestone Threshold</font>&#8221; has the meaning set forth in <u>Section 6.14</u> (Commercial Milestones).</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Annual Net Sales-Based Milestone Payment</font>&#8221; has the meaning set forth in <u>Section 6.14</u> (Commercial Milestones).</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">APOL1</font>&#8221; means the mRNA or pre-RNA of the human apolipoprotein L1 gene (NCBI Gene ID: 8542; Ensembl Gene ID: ENSG00000100342), including any alternative
        splice variants, mutants, polymorphisms or fragments.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">APOL1 Product</font>&#8221; has the meaning set forth in the <u>Recitals</u> of the Fourth Amendment.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">AstraZeneca Collaboration Intellectual Property</font>&#8221; means any Know-How and Patent Rights that were discovered, developed, invented or created by or on behalf
        of AstraZeneca in connection with (a) the performance of any Collaboration Plan and/or (b) if, following the Fourth Amendment Effective Date and during the Agreement Term, the Parties mutually agree, in writing, upon a Cooperation Plan, the
        performance of activities under such plan, in each case ((a) and (b)) including AstraZeneca&#8217;s interest in any Jointly-Owned Collaboration Technology and excluding any AstraZeneca Product-Specific Patents.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">AstraZeneca Field</font>&#8221; means [***].</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Collaboration Intellectual Property</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Collaboration Technology</font>&#8221; means, collectively,
        AstraZeneca Collaboration Intellectual Property, Ionis Collaboration Intellectual Property and Jointly-Owned Collaboration Technology.&#160; For the avoidance of doubt, [***].</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Collaboration Products</font>&#8221; has the meaning set forth in the <u>Recitals</u> of the Fourth Amendment.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Compound</font>&#8221; means (i) any ASO that is designed to bind to a Collaboration Target, where such ASO is discovered by Ionis prior to the date on which such
        Target becomes a High Interest Target (or, with respect to [***], the Effective Date), or in the performance of a Collaboration Plan or (ii) any [***] Compound; and in each case any salt, hydrate, solvate or pro-drug thereof.&#160; For clarity, such
        ASOs will be different Compounds if they have different sequences of nucleotides, use different modified nucleotides (including a different backbone, sugar moiety or base modification), or if they employ different Conjugate Technology, such as
        GalNAc.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Cooperation Plan</font>&#8221; has the meaning set forth in <u>Section 4.11</u>.</div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">23</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Exclusive Target</font>&#8221; means (i) any Reserved Target, (ii) High Interest Target, (iii) any Collaboration Target, or (iv) [***].&#160; The term &#8220;<font style="font-weight: bold; font-style: italic;">Exclusive Targets</font>&#8221; means collectively the Reserved Targets, High Interest Targets, Collaboration Targets, and [***].</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Fourth Amendment</font>&#8221; has the meaning set forth in the <u>Preamble</u> of the Fourth Amendment.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Fourth Amendment Effective Date</font>&#8221; has the meaning set forth in the <u>Preamble</u> of the Fourth Amendment.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Fourth Amendment Products</font>&#8221; means the APOL1 Products, [***] Products, [***] Products, or PNPLA3 Products, collectively or individually, as the context
        requires.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221; has the meaning set forth in the <u>Preamble</u> of the Fourth Amendment.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Intellectual Property</font>&#8221; means any Know-How and Patent Rights that were discovered, developed, invented or created by or on behalf of
        Ionis in connection with (a) the performance of any Collaboration Plan and/or (b) if, following the Fourth Amendment Effective Date and during the Agreement Term, the Parties mutually agree, in writing, upon a Cooperation Plan, the performance of
        activities under such plan, in each case ((a) and (b)) including Ionis&#8217; interest in any Jointly-Owned Collaboration Technology and excluding any Ionis Product-Specific Patents.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Field</font>&#8221; means [***].</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Jointly-Owned Collaboration Know-How</font>&#8221; means Know-How discovered, developed, invented or created jointly by or on behalf of both Parties or their respective
        Affiliates or Third Parties acting on their behalf in connection with (a) the performance of any Collaboration Plan and/or (b) if, following the Fourth Amendment Effective Date and during the Agreement Term, the Parties mutually agree, in writing,
        upon a Cooperation Plan, the performance of activities under such plan, in each case ((a) and (b)) that is necessary or useful to Develop, Manufacture or Commercialize a Product in the Field.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Knowledge</font>&#8221; means the good faith, actual understanding of the facts and information by a Party&#8217;s or any of its Affiliate&#8217;s executive officers and their
        attorneys employed in their Legal Department and Patent Department as of the Effective Date, a Bring-Down Date or the Fourth Amendment Effective Date (as applicable); <font style="font-style: italic;">provided that</font>, with respect to
        information regarding the status of Patent Rights or other intellectual property rights, &#8220;<font style="font-style: italic;">Knowledge</font>&#8221; means the good faith, actual understanding of the facts and information by a Party&#8217;s or any of its
        Affiliate&#8217;s executive officers and their attorneys employed in their Legal Department and Patent Department as of the Effective Date, a Bring-Down Date or the Fourth Amendment Effective Date (as applicable) after performing a diligent investigation
        with respect to such facts and information as is customary in the conduct of its business with respect to such Patent Rights or other intellectual property rights (and not, for clarity, a diligent investigation solely in connection with this
        Agreement).</div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">24</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Licensed Program</font>&#8221; means (i) a Collaboration Program following exercise of the applicable Collaboration Program License Right or (ii) the [***] Licensed
        Program; <font style="font-style: italic;">provided that </font>in all cases ((i) and (ii)), for so long as the applicable license under <u>Section 4.1.1</u> for such program is effective.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Minimum Third Party Payments</font>&#8221; means [***].</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">[***]</font>&#8221; means [***].</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">[***] Compound</font>&#8221; means any ASO that is designed to bind to [***], where such ASO was discovered by Ionis prior to the Fourth Amendment Effective Date,
        including [***] which is specifically described in <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 8A</u> (the &#8220;<font style="font-weight: bold; font-style: italic;">Lead [***] Compound</font>&#8221;) and [***] which is specifically
        described in <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 8B</u> (the &#8220;<font style="font-weight: bold; font-style: italic;">Secondary [***] Compound</font>&#8221;).</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">[***] Licensed Program</font>&#8221; means the program for [***] Products under the Agreement.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">[***] Product</font>&#8221; means a Product that comprises a Compound designed to bind to [***].</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Other Joint Technology</font>&#8221; has the meaning set forth in <u>Section 7.1.4</u>.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">[***]</font>&#8221; means [***].</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">[***] Letter Agreement</font>&#8221; has the meaning set forth in the <u>Preamble</u> of the Fourth Amendment.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">[***] Product</font>&#8221; has the meaning set forth in the <u>Recitals</u> of the Fourth Amendment.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">PNPLA3</font>&#8221; means the mRNA or pre-RNA of the human patatin like phospholipase domain containing 3 gene (NCBI Gene ID: 80339; Ensembl Gene ID: ENSG00000100344),
        including any alternative splice variants, mutants, polymorphisms or fragments.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">PNPLA3 Product</font>&#8221; has the meaning set forth in the <u>Recitals</u> of the Fourth Amendment.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">25</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt;"><u> 4A</u></font></div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">Ionis Core Technology Patents</div>
      <div>&#160;</div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt;">(</font><font style="font-size: 10pt; font-variant: small-caps;">With Respect to the Lead </font><font style="font-size: 10pt;">[***]</font><font style="font-size: 10pt; font-variant: small-caps;"> Compound and the Secondary </font><font style="font-size: 10pt;">[***]</font><font style="font-size: 10pt; font-variant: small-caps;"> Compound</font><font style="font-size: 10pt;">)</font></div>
      <div>&#160;</div>
      <div style="text-align: center;">[***]</div>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">26</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt;"><u> 5A</u></font></div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">Ionis Manufacturing and Analytical Patents</div>
      <div>&#160;</div>
      <div style="text-align: center; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">(</font><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;">With Respect to the Lead </font><font style="font-size: 10pt; font-weight: bold;">[***]</font><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;"> Compound and the Secondary </font><font style="font-size: 10pt;">[***]</font><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;"> Compound</font><font style="font-size: 10pt; font-weight: bold;">)</font></div>
      <div>&#160;</div>
      <div style="text-align: center;">[***]</div>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">27</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt;"><u> 6A</u></font></div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">Ionis Product-Specific Patents</div>
      <div>&#160;</div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt;">(</font><font style="font-size: 10pt; font-variant: small-caps;">With Respect to the </font><font style="font-size: 10pt;">[***]</font><font style="font-size: 10pt; font-variant: small-caps;"> Products</font><font style="font-size: 10pt;">)</font></div>
      <div>&#160;</div>
      <div style="text-align: center;">[***]<br>
        <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">28</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt;"><u> 7A</u></font></div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;">Prior Agreements</div>
      <div><br>
      </div>
      <div style="text-align: center;">[***]</div>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">29</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt;"><u> 8A</u></font></div>
      <div><br>
      </div>
      <div style="text-align: center; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">Lead </font><font style="font-size: 10pt;">[***]<font style="font-weight: bold;"> Compound</font></font></div>
      <div><br>
      </div>
      <div style="text-align: center;">(Also known as [***]<font style="font-style: italic;">)</font></div>
      <div><br>
      </div>
      <div style="text-align: center;">[***]</div>
      <div style="text-align: center;"> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">30</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt;"><u> 8B</u></font></div>
      <div><br>
      </div>
      <div style="text-align: center; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">Secondary </font><font style="font-size: 10pt;">[***]<font style="font-weight: bold;"> Compound</font></font></div>
      <div><br>
      </div>
      <div style="text-align: center;">(Also known as [***]<font style="font-style: italic;">)</font></div>
      <div><br>
      </div>
      <div style="text-align: center;">[***]</div>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">31</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix</u></font><font style="font-size: 10pt;"><u> 9</u></font></div>
      <div><br>
      </div>
      <div style="text-align: center; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">Lead </font><font style="font-size: 10pt;">[***]<font style="font-weight: bold;"> Compound Technology Transfer Plan</font></font></div>
      <div><br>
      </div>
      <div style="text-align: center;">[***]</div>
      <div style="text-align: center;"> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">32</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Schedule</u></font><font style="font-size: 10pt;"><u> 6.4</u></font></div>
      <div><br>
      </div>
      <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;">Table 1a</font><font style="font-size: 10pt; font-weight: bold;">:</font><font style="font-size: 10pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;[***]<font style="font-weight: bold;"> Licensed Program Development Milestones</font></font></div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="z4639b65105de45828c9ea66e0b9fe21f">

          <tr>
            <td style="width: 24.99%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Product Milestone</div>
              <div style="text-align: center; font-weight: bold;">Event</div>
            </td>
            <td style="width: 24.99%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">CVRM Agreement</div>
              <div style="text-align: center; font-weight: bold;">Milestone Payment</div>
              <div style="text-align: center; font-weight: bold;">(M)</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Total Milestone</div>
              <div style="text-align: center; font-weight: bold;">Payment (M)</div>
            </td>
          </tr>
          <tr>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 24.99%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center; font-weight: bold;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 24.99%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 24.99%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center; font-weight: bold;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center; font-weight: bold;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center; font-weight: bold;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 24.99%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center; font-weight: bold;">$[***]</div>
            </td>
          </tr>

      </table>
      <div>[***]</div>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">33</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Schedule</u></font><font style="font-size: 10pt;"><u> 6.7.1</u></font></div>
      <div><br>
      </div>
      <div style="font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;">Table</font><font style="font-size: 10pt;"> 3<font style="font-variant: small-caps;">a</font>: [***] Licensed Program Royalties</font></div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="z682497ddbc444f6d9afabdd4edf365a3">

          <tr>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 32.67%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">Annual Worldwide Net Sales </div>
              <div style="text-align: center;">of Products from a Licensed </div>
              <div style="text-align: center;">Program</div>
            </td>
            <td style="width: 22.44%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">CVRM</div>
              <div style="text-align: center; font-weight: bold;"> Agreement</div>
              <div style="text-align: center; font-weight: bold;">Royalty Rate</div>
            </td>
            <td style="width: 22.44%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">[***]</div>
            </td>
            <td style="width: 22.45%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Total Royalty</div>
              <div style="text-align: center; font-weight: bold;">Rate</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 32.67%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>For the portion of Annual Worldwide Net Sales &lt; $[***]</div>
            </td>
            <td style="width: 22.44%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]%</div>
            </td>
            <td style="width: 22.44%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 22.45%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">[***]%</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 32.67%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>For the portion of Annual Worldwide Net Sales &#8805; $[***] but &lt; $[***]</div>
            </td>
            <td style="width: 22.44%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]%</div>
            </td>
            <td style="width: 22.44%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 22.45%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">[***]%</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 32.67%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>For the portion of Annual Worldwide Net Sales &#8805;&#160;$[***]</div>
            </td>
            <td style="width: 22.44%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]%</div>
            </td>
            <td style="width: 22.44%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 22.45%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">[***]%</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">34</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Schedule</u></font><font style="font-size: 10pt;"><u> 6.14</u></font></div>
      <div><br>
      </div>
      <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;">Table</font><font style="font-size: 10pt; font-weight: bold;"> 2</font><font style="font-size: 10pt; font-weight: bold; font-variant: small-caps;">a</font><font style="font-size: 10pt; font-weight: bold;">: </font><font style="font-size: 10pt;">[***]<font style="font-weight: bold;"> Licensed Program Sales Milestones</font></font></div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="zf363fc1c4a7545468d324bda1009e2d2">

          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 25.94%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Sales Milestone</div>
              <div style="text-align: center; font-weight: bold;">Event</div>
            </td>
            <td style="width: 24.05%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">CVRM Agreement</div>
              <div style="text-align: center; font-weight: bold;">Milestone Payment</div>
              <div style="text-align: center; font-weight: bold;">(M)</div>
            </td>
            <td style="width: 25.01%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Total Milestone</div>
              <div style="text-align: center; font-weight: bold;">Payment (M)</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 25.94%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>Cumulative Net Sales</div>
              <div>&#8805;&#160;$[***]</div>
            </td>
            <td style="width: 24.05%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">$</font><font style="font-size: 10pt;">[***]<font style="font-weight: bold;">*</font></font></div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 25.94%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>Cumulative Net Sales</div>
              <div>&#8805;&#160;$[***]</div>
            </td>
            <td style="width: 24.05%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 25.01%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">$</font><font style="font-size: 10pt;">[***]<font style="font-weight: bold;">*</font></font></div>
            </td>
          </tr>

      </table>
      <div>[***]</div>
      <div> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">35</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        <div class="BRPFPageHeader" style="width: 100%;">
          <div><font style="font-weight: normal; font-style: italic;">Final Execution Version</font></div>
        </div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-variant: small-caps;"><u>Schedule</u></font><font style="font-size: 10pt;"><u> 8.2.18</u></font></div>
      <div><br>
      </div>
      <div style="text-align: center;">[***]</div>
      <div style="text-align: center;"> <br>
      </div>
      <div style="text-align: center;"> <br>
      </div>
      <div style="text-align: center;"> <font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">36</font></div>
      <div style="text-align: center;">
        <hr noshade="noshade" align="center" style="height: 2px; color: #000000; background-color: #000000; margin-left: auto; margin-right: auto; border: none;"></div>
    </div>
  </div>
</body>
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</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-19
<SEQUENCE>3
<FILENAME>exhibit19.htm
<DESCRIPTION>EXHIBIT 19
<TEXT>
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  <head>
    <title></title>
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  <div>
    <div>
      <div style="text-align: right; font-weight: bold;">Exhibit 19</div>
      <div><br>
      </div>
    </div>
    <div>
      <div style="text-align: justify; font-weight: bold;">PUBLIC COMPANY OBLIGATIONS</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-size: 12pt;"><font style="font-size: 10pt; color: rgb(51, 51, 51);">Ionis Pharmaceuticals, Inc. (&#8220;Ionis&#8221;) </font><font style="font-size: 10pt;">is a public company, which means it is owned by its stockholders and its securities are publicly traded. Every Ionis employee has an obligation to protect Ionis&#8217; value and assets. When you started employment at Ionis, you signed an
          Employee Confidential Information and Invention Agreement.&#160; In this agreement, you promised to protect Ionis&#8217; confidential information and trade secrets by not disclosing this information to unauthorized persons.&#160; It is your responsibility to
          fully understand and comply with this agreement.</font></div>
      <div>&#160;</div>
      <div style="text-align: justify;">It is also your obligation to understand certain actions that you cannot take, either because to do so is unlawful for the employees of a public company or
        because to do so could harm Ionis.&#160; Every employee and non-employee director has the individual responsibility to comply with this policy.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-weight: bold;">Insider Trading</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-weight: bold;">Prohibited Activities</div>
      <div>&#160;</div>
      <div style="text-align: justify;">During the course of your employment, you may receive material information that is not yet publicly available (&#8220;material nonpublic information&#8221;) about Ionis
        or about other publicly traded companies with which Ionis has business dealings.&#160; Because of your access to this information, you may be in a position to profit financially by buying or selling or in some other way dealing in Ionis&#8217; securities or
        the securities of another publicly traded company.&#160; Similarly, you may be in a position to benefit financially or otherwise by passing this information on to some other person.&#160; Whether you personally benefit or another person benefits, this is
        considered &#8220;insider trading&#8221; and is illegal.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">The following activities are prohibited:</div>
      <div><br>
      </div>
    </div>
    <div>
      <table cellspacing="0" cellpadding="0" id="zb4b34f784f324d069eaa490df1208def" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>No unauthorized disclosure.&#160; You may not disclose material nonpublic information to anyone at Ionis who is not authorized to access it or to anyone outside Ionis.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z3115ca3b79204047912d5d0efd9e8ceb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>No trading in Ionis securities with material nonpublic information.&#160; When you have access to material nonpublic information about Ionis, you may not buy or sell Ionis securities
                regardless of the amount nor may you encourage or discourage others from trading Ionis&#8217; securities.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z6a5ec7d21436419884b752c7a06162ec" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>No trading in Ionis&#8217; partner&#8217;s securities with material nonpublic information.&#160; When you have access to material nonpublic information about other publicly traded companies with which
                Ionis has a business relationship, you may not buy or sell securities in the applicable company regardless of the amount nor may you encourage or discourage others from trading that company&#8217;s securities.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
    </div>
    <div>
      <table cellspacing="0" cellpadding="0" id="zc2d3f3fb7439424898d89dda1b571437" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>No establishment of Rule 10b5-1 Plans with material nonpublic information.&#160; When you have access to material nonpublic information about Ionis, you may not establish a Rule 10b5-1 Plan.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div class="BRPFPageBreak" style="page-break-after: always;">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div>
      <div style="text-align: justify;">The prohibition against insider trading is absolute and the U.S. federal securities laws do not recognize any mitigating circumstances to insider trading. It
        also applies to transactions that may be necessary or justifiable for independent reasons (such as the need to raise money for an emergency expenditure) and to transactions with a small dollar value.&#160; All that matters is whether you are aware of
        any material nonpublic information relating to Ionis or its partner(s) at the time of the transaction. In some circumstances, you may need to forgo a planned transaction even if you planned it before becoming aware of the material nonpublic
        information. Even if you believe you may suffer an economic loss or sacrifice an anticipated profit by waiting to trade, you must wait.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">It is also important to note that the laws prohibiting insider trading are not limited to trading by the insider alone; advising others to trade on the basis
        of material nonpublic information is illegal and prohibited by this policy. Liability in such cases can extend both to the &#8220;tippee&#8221;&#8212;the person to whom the insider disclosed material nonpublic information&#8212;and to the &#8220;tipper,&#8221; the insider.&#160; In such
        cases, you can be held liable for your own transactions, as well as the transactions by a tippee and even the transactions of a tippee&#8217;s tippee. These prohibitions against trading when you have access to material nonpublic information also apply to
        members of your household and businesses and other entities you control.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-weight: bold;">Examples of Material Nonpublic Information</div>
      <div>&#160;</div>
      <div style="text-align: justify;">As a practical matter, it is sometimes difficult to determine whether you possess material nonpublic information.&#160; The key to determining whether nonpublic
        information you possess about a public company is material nonpublic information is whether public disclosure of the information would be likely to affect the market price of the company&#8217;s securities or if a reasonable investor who is considering
        trading in that company&#8217;s securities would consider the information important to its decision to trade.&#160; If the information makes you want to trade, it would probably have the same effect on others.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">While it may be difficult under this standard to determine whether certain information is material nonpublic information, there are categories of information
        that are particularly sensitive and therefore more likely to be considered material nonpublic information.&#160; Either positive or negative information may be material nonpublic information, and the information can be material nonpublic information
        with respect to both Ionis&#8217; securities and Ionis&#8217; partner&#8217;s securities.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">Examples include, but are not limited to:</div>
      <div>&#160;</div>
    </div>
    <div>
      <table cellspacing="0" cellpadding="0" id="z2ae2cecdf1ae47e7b3435e01d334ec3c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>status of regulatory approvals;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zc02213aa85c4418e8c16f3908ee2c481" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>results of clinical trials involving Ionis&#8217; or another company&#8217;s drug.&#160; Note this information could prohibit trading in both Ionis&#8217; and the partner company&#8217;s stock;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb9edc9d9bac740279004bae1d8b2fa2d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>communications, whether written or oral, from the FDA or other regulatory authority regarding Ionis&#8217; or another company&#8217;s drug;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z0687583a473e498a93b43cde33812777" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>existing or potential partnering transactions related to Ionis&#8217; programs including progress under the transactions and financial consequences;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf998f9f8731c45dcb39ed7e9bb2a3501" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>potential acquisitions or dispositions of product candidates, technologies or businesses by Ionis or another company;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div class="BRPFPageBreak" style="page-break-after: always;">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div>
      <table cellspacing="0" cellpadding="0" id="zc2f440a25636487f8da304333d072a86" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>new equity or debt offerings or repurchases by Ionis;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z53ecf2786acc4e398b1c516b3220bb7b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>financial results (annual, quarterly or interim), forecasts and commercial sales data;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z09f49255841148f2bc83b82af5f09145" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>adjustments to Ionis&#8217; financial guidance;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf8dabc918fdf4d529416b9924896de13" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>litigation or settlements; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
    </div>
    <div>
      <table cellspacing="0" cellpadding="0" id="zd88160995ec44043928b5410acabd551" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>a disruption in Ionis&#8217; operations or breach or unauthorized access of its property or assets, including its facilities and information technology infrastructure.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
    </div>
    <div>
      <div style="text-align: justify;">You should discuss questions regarding whether nonpublic information is material nonpublic information with Ionis&#8217; CFO or General Counsel.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-weight: bold;">Blackout Policy</div>
      <div>&#160;</div>
      <div style="text-align: justify;">In addition to the prohibition against trading while you possess material nonpublic information, Ionis, through its CFO or General Counsel, may impose
        certain blackout periods during which employees will be prohibited from trading in Ionis&#8217; securities, unless such trades are made under a previously adopted, valid Rule 10b5-1 Plan that complies with Ionis&#8217; policies.&#160; Generally, Ionis will impose a
        trading blackout period during the following times:</div>
      <div>&#160;</div>
    </div>
    <div>
      <table cellspacing="0" cellpadding="0" id="z8767c8af12094aabbfaaf4562552901a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>when Ionis unblinds the data (or if an open label study, completes the primary statistical analyses plan) for a clinical study (for a preliminary or final analysis) for one of Ionis&#8217;
                drugs where Ionis&#8217; CFO and General Counsel have determined the results of such study are material nonpublic information until the top line results of such study are publicly disclosed by Ionis;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z71e243327d10423cad16cfec8138063c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>when Ionis reasonably believes that a significant partnering transaction related to one or more of Ionis&#8217; programs is imminent until Ionis publicly discloses such transaction; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
    </div>
    <div>
      <table cellspacing="0" cellpadding="0" id="zf1f86f8de8ad4e50b4833410d9356cc5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>on the first business day following the end of the recently completed fiscal year or quarter until Ionis publicly discloses its financial results for such year or quarter.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
    </div>
    <div>
      <div style="text-align: justify;">In addition, Ionis may impose additional blackout periods if Ionis&#8217; CFO or General Counsel believes material nonpublic information exists that requires
        imposing a blackout period to avoid the potential for, or the perception of, insider trading.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">Generally, each blackout period will end at market open the trading day following public disclosure of Ionis&#8217; financial results for the year or quarter.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">The fact that Ionis has imposed a blackout period is Ionis&#8217; confidential information and may not be disclosed outside Ionis.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">Any time a blackout period is in effect, Ionis will notify its employees, and Ionis&#8217; Stock Plan Administrator is authorized to block or reverse transactions
        in Ionis&#8217; securities that violate this policy.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-style: italic; font-weight: bold;">Please remember, you cannot assume it is OK to trade simply because no blackout period applies.&#160; Even when there is no
        blackout, you still may possess material nonpublic information that precludes you from trading.&#160; As a result, each time you wish to trade in the absence of a blackout, you still must use good judgment and refrain from trading on the basis of
        material nonpublic information.</div>
      <div>&#160;</div>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div class="BRPFPageBreak" style="page-break-after: always;">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div>
      <div style="text-align: justify; font-weight: bold;">Rule 10b5-1 Plans Required for CEO and Members of the Operating Committee; Optional for All Other Employees</div>
      <div>&#160;</div>
      <div style="text-align: justify;">The CEO and all members of Ionis&#8217; Operating Committee can only trade (buy or sell) Ionis&#8217; securities using an Ionis approved Rule 10b5-1 Plan.&#160; Please note
        that this restriction applies not only to the individual, but also to members of such individual&#8217;s household and businesses or other entities the individual controls.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">All other employees may choose to trade Ionis&#8217; securities using an Ionis approved Rule 10b5-1 Plan.&#160; If an employee chooses to use a Rule 10b5-1 Plan, then
        such employee may not trade Ionis&#8217; securities outside of a Rule 10b5-1 Plan for at least 12 months following the date on which all of such employee&#8217;s Rule 10b5-1 Plans have expired or been terminated.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">Employees may only establish a Rule 10b5-1 Plan at a time when they are not in possession of material nonpublic information and when no blackout period
        applies.&#160; Please contact Ionis&#8217; Stock Plan Administrator or General Counsel if you have any questions regarding how to implement a Rule 10b5-1 Plan.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-weight: bold;">Pre-Clearance Procedures for Non-Employee Directors</div>
      <div>&#160;</div>
      <div style="text-align: justify;">Ionis&#8217; non-employee Directors are strongly encouraged to trade Ionis&#8217; securities using a Rule 10b5-1 Plan approved by Ionis.&#160; To avoid the potential
        appearance of inappropriate trading, Ionis&#8217; non-employee Directors may not trade in Ionis&#8217; securities without first contacting Ionis&#8217; General Counsel and obtaining pre-clearance from such officer to trade, unless such trades are made pursuant to a
        Rule 10b5-1 Plan approved by Ionis.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-weight: bold;">Certain Transactions Not Subject to this Policy</div>
      <div>&#160;</div>
      <div style="text-align: justify;">The exercise of stock options for cash under Ionis&#8217; stock option plans, purchases under Ionis&#8217; Employee Stock Purchase Plan (&#8220;ESPP&#8221;), and transactions that
        are automatically effected by Ionis&#8217; Stock Plan Administrator in connection with the vesting and release of restricted stock units (&#8220;RSUs&#8221;) are exempt from this policy, since the other party to these transactions is Ionis itself, or the timing of
        the transaction is fixed and you do not control the timing or execution of the transaction.&#160; This exemption does not apply to the sale by you of any shares issued upon an option exercise, ESPP purchase, or RSU release, and it does not apply to a
        cashless exercise of options, which is accomplished by a sale of a portion of the shares issued upon exercise of an option.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">If a Rule 10b5-1 Plan is properly established, purchases and sales of Ionis&#8217; securities pursuant to that Plan are not subject to this policy.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">In addition, bona fide gifts and charitable donations of Ionis&#8217; securities are exempt from this policy.</div>
      <div>&#160;</div>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div class="BRPFPageBreak" style="page-break-after: always;">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div>
      <div style="text-align: justify; font-weight: bold;">Annual Training Required</div>
      <div>&#160;</div>
      <div style="text-align: justify;">Each employee must complete Ionis&#8217; approved insider trading training at least once every twelve months.&#160; Failure to timely complete the training could result
        in suspended trading privileges under this policy until training is completed, and other disciplinary action.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-weight: bold;">Hedging, Pledging and Other Speculative Transactions Prohibited</div>
      <div>&#160;</div>
      <div style="text-align: justify;">None of Ionis&#8217; employees or non-employee directors may engage in any type of hedging against Ionis&#8217; stock, including short sales and derivatives such as put
        or call options, swaps, forwards, and futures, or other inherently speculative transactions with respect to Ionis&#8217; securities at any time.&#160; You are also discouraged from engaging in these types of transactions with respect to Ionis&#8217; partners&#8217;
        securities.&#160; In addition, none of Ionis&#8217; employees or non-employee directors may pledge as collateral any of Ionis&#8217; securities, including without limitation, making any offer to margin or borrowing against such securities, at any time.&#160; These
        practices are prohibited by you, members of your household and businesses or other entities you control.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-weight: bold;">Policy Duration</div>
      <div>&#160;</div>
      <div style="text-align: justify;">This policy continues to apply to your transactions in Ionis&#8217; securities and the securities of other applicable public companies even after your relationship
        with Ionis has ended. If you are aware of material nonpublic information when your relationship with Ionis ends, you may not trade Ionis&#8217; securities or the securities of other applicable publicly traded companies until the material nonpublic
        information has been publicly disseminated or is no longer material.&#160; Further, if you leave Ionis during a trading blackout period, then you may not trade Ionis&#8217; securities or the securities of other applicable companies until such trading blackout
        period has ended.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-weight: bold;">Individual Responsibility</div>
      <div>&#160;</div>
      <div style="text-align: justify;">Persons subject to this policy have ethical and legal obligations to maintain the confidentiality of information about Ionis and to not engage in
        transactions in Ionis&#8217; securities or the securities of other applicable public companies while aware of material nonpublic information, as more specifically set forth in this policy. In all cases, the responsibility for determining whether an
        individual is aware of material nonpublic information rests with that individual, and any action on the part of Ionis or any employee or non-employee director of Ionis pursuant to this policy does not in any way constitute legal advice or insulate
        an individual from liability under applicable securities laws. You could be subject to severe legal penalties and disciplinary action by Ionis for any conduct prohibited by this policy or applicable securities laws.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-weight: bold;">Amendments</div>
      <div>&#160;</div>
      <div style="text-align: justify;">Ionis is committed to continuously reviewing and updating its policies and procedures. Ionis therefore reserves the right to amend, alter or terminate this
        policy at any time and for any reason.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-weight: bold;">The Internet and Social Media Platforms</div>
      <div>&#160;</div>
      <div style="text-align: justify;">Ionis has social media guidelines that establish guiding principles that govern communication about Ionis and Ionis&#8217; stock on all social media platforms.
        Please refer to these guidelines on the Policies &amp; Procedures section of the IoniSphere.</div>
      <div>&#160;</div>
      <div><br>
      </div>
      <div>
        <hr noshade="noshade" align="center" style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;"></div>
    </div>
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</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-23.1
<SEQUENCE>4
<FILENAME>exhibit23-1.htm
<DESCRIPTION>EXHIBIT 23.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 25.1.1.5279
         Copyright 1995 - 2025 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:b8cd2a2a-2f7b-470b-8887-e5b31a337448"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit 23.1</div><div style="text-align: center;"><br></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM</div><div style="margin-top: 5pt; margin-bottom: 5pt;"><br></div><div style="text-align: left; margin-top: 5pt; margin-bottom: 5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consent to the incorporation by reference in the following Registration Statements:</div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 5pt; margin-bottom: 5pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z90824a68fa694785971fbd4990d24813"><tr><td style="width: 36pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 18pt; margin-top: 5pt; margin-bottom: 5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: left; text-indent: 36pt; margin-top: 5pt; margin-bottom: 5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Registration Statement (Form S-3 No. 333-275741) of Ionis Pharmaceuticals, Inc., and</div></td></tr></table><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 5pt; margin-bottom: 5pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z716a0e156ecd47c183a6f83b303b076e"><tr><td style="width: 36pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 18pt; margin-top: 5pt; margin-bottom: 5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: left; text-indent: 36pt; margin-top: 5pt; margin-bottom: 5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Registration Statements (Form S-8 Nos. 333-05825, 333-55683, 333-40336, 333-59296, 333-91572, 333-106859, 333-116962, 333-125911, 333-133853, 333-142777, 333-151996, 333-160269, 333-168674, 333-176136, 333-184788, 333-190408, 333-207900, 333-219801, 333-233143, 333-242386, 333-251855, 333-258503, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">333-273902 and 333-281242</font>) of Ionis Pharmaceuticals, Inc.;</div></td></tr></table><div style="text-align: left; margin-top: 5pt; margin-bottom: 5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">of our reports dated February 19, 2025, with respect to the consolidated financial statements of Ionis Pharmaceuticals, Inc. and the effectiveness of internal control over financial reporting of Ionis Pharmaceuticals, Inc. included in this Annual Report (Form 10-K) of Ionis Pharmaceuticals, Inc. for the year ended December 31, 2024.</div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z7c9fb007abb140f0bde8b8f819de3425"><tr><td style="width: 50.57%; vertical-align: top;"><div>&#160;</div><div>&#160;</div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ Ernst &amp; Young LLP</div><div>&#160;</div></td><td style="width: 49.43%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 50.57%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">San Diego, California</div></td><td style="width: 49.43%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 50.57%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 19, 2025</div></td><td style="width: 49.43%; vertical-align: top;">&#160;</td></tr></table><div style="text-align: left;"><br></div></div></body></html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-31.1
<SEQUENCE>5
<FILENAME>exhibit31-1.htm
<DESCRIPTION>EXHIBIT 31.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 25.1.1.5279
         Copyright 1995 - 2025 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:27688458-8a95-448c-9822-a3a5e0da6065"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit 31.1</div><div><br></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">I, Brett P. Monia, certify that:</div><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z77616025b0044d8fa1271b308954b8e6"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">I have reviewed this Annual Report on Form 10-K of Ionis Pharmaceuticals, Inc.;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z9c480025c64044958865db0d911e1ab7"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on my knowledge, this annual report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this annual report;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc6fa3c291acf4cf6b441d44977a5e315"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on my knowledge, the consolidated financial statements, and other financial information included in this annual report, fairly present in all material respects the financial condition, consolidated results of operations and consolidated cash flows of the registrant as of, and for, the periods presented in this annual report;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z807e4a2c44744620ba50db5940fcb20a"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The registrant&#8217;s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z0ae8318d0d8144399a72c50cab57a5f4"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z0c1ee3b748a044d4b1b322ec5311c86e"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">b)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z356aedf2d57c4f88915ccf4c833b193a"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">c)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Evaluated the effectiveness of the registrant&#8217;s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zf60afcb268aa4ee69098eb0e441eb4ed"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">d)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Disclosed in this report any change in the registrant&#8217;s internal control over financial reporting that occurred during the registrant&#8217;s most recent fiscal quarter (the registrant&#8217;s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant&#8217;s internal control over financial reporting; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zd25d8372592944278b05aedefb6af341"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The registrant&#8217;s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant&#8217;s auditors and the audit committee of registrant&#8217;s board of directors (or persons performing the equivalent functions):</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z5b45638bd483429e97addbb7efb13de7"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant&#8217;s ability to record, process, summarize and report financial information; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z90135640fcad4a30b51f80d4ca5025f7"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">b)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant&#8217;s internal control over financial reporting.</div></td></tr></table><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;&#160;</div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z4adbdb70bfb043ca8d48ccbf081d8e39"><tr><td style="width: 41.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dated: February 19, 2025</div></td><td style="width: 58.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 58.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.41%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ BRETT P. MONIA</div></td><td style="width: 58.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia, Ph.D.</div></td><td style="width: 58.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Executive Officer</div></td><td style="width: 58.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr></table><div><br></div></div></body></html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-31.2
<SEQUENCE>6
<FILENAME>exhibit31-2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 25.1.1.5279
         Copyright 1995 - 2025 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:f325a129-9b94-442a-a705-509884803066"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit 31.2</div><div><br></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">I, Elizabeth L. 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  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:6efc6d20-d43f-45b4-aa04-090d35475d75"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit 32.1</div><div><br></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pursuant to the requirement set forth in Rule&#160;13a-14(b)&#160;of the Securities Exchange Act of 1934, as amended (the &#8220;Exchange Act&#8221;), and Section&#160;1350 of Chapter 63 of Title 18 of the United States Code (18&#160;U.S.C. &#167;1350),&#160; Brett P. Monia, the Chief Executive Officer of Ionis Pharmaceuticals, Inc., (the &#8220;Company&#8221;), and Elizabeth L. 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        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/LegalProceedings" id="LegalProceedings">
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        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/SegmentInformation" id="SegmentInformation">
        <link:definition>061200 - Disclosure - Segment Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/FourthQuarterFinancialDataUnaudited" id="FourthQuarterFinancialDataUnaudited">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/CybersecurityRiskManagementAndStrategyDisclosure" id="CybersecurityRiskManagementAndStrategyDisclosure">
        <link:definition>061400 - Disclosure - Cybersecurity Risk Management and Strategy Disclosure</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/InsiderTradingArrangements" id="InsiderTradingArrangements">
        <link:definition>061500 - Disclosure - Insider Trading Arrangements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/OrganizationAndSignificantAccountingPoliciesPolicies" id="OrganizationAndSignificantAccountingPoliciesPolicies">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/OrganizationAndSignificantAccountingPoliciesTables" id="OrganizationAndSignificantAccountingPoliciesTables">
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        <link:definition>080100 - Disclosure - Organization and Significant Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/SupplementalFinancialDataTables" id="SupplementalFinancialDataTables">
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        <link:definition>080200 - Disclosure - Supplemental Financial Data (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/RevenuesTables" id="RevenuesTables">
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        <link:definition>080300 - Disclosure - Revenues (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/CollaborativeArrangementsAndLicensingAgreementsTables" id="CollaborativeArrangementsAndLicensingAgreementsTables">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/InvestmentsTables" id="InvestmentsTables">
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        <link:definition>080500 - Disclosure - Investments (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/FairValueMeasurementsTables" id="FairValueMeasurementsTables">
        <!--Parent Role: Fair Value Measurements-->
        <link:definition>080600 - Disclosure - Fair Value Measurements (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/LongtermObligationsAndCommitmentsTables" id="LongtermObligationsAndCommitmentsTables">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/StockholdersEquityTables" id="StockholdersEquityTables">
        <!--Parent Role: Stockholders' Equity-->
        <link:definition>080800 - Disclosure - Stockholders' Equity (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/IncomeTaxesTables" id="IncomeTaxesTables">
        <!--Parent Role: Income Taxes-->
        <link:definition>080900 - Disclosure - Income Taxes (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionis.com/role/SegmentInformationTables" id="SegmentInformationTables">
        <!--Parent Role: Segment Information-->
        <link:definition>081200 - Disclosure - Segment Information (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/FourthQuarterFinancialDataUnauditedTables" id="FourthQuarterFinancialDataUnauditedTables">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/OrganizationAndSignificantAccountingPoliciesOrganizationAndBusinessActivityDetails" id="OrganizationAndSignificantAccountingPoliciesOrganizationAndBusinessActivityDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/OrganizationAndSignificantAccountingPoliciesContractsReceivableDetails" id="OrganizationAndSignificantAccountingPoliciesContractsReceivableDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:definition>090300 - Disclosure - Revenues (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails" id="CollaborativeArrangementsAndLicensingAgreementsBiogenDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails" id="CollaborativeArrangementsAndLicensingAgreementsGskDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails" id="CollaborativeArrangementsAndLicensingAgreementsNovartisDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails" id="CollaborativeArrangementsAndLicensingAgreementsRocheDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/CollaborativeArrangementsAndLicensingAgreementsOtsukaDetails" id="CollaborativeArrangementsAndLicensingAgreementsOtsukaDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/CollaborativeArrangementsAndLicensingAgreementsPtcTherapeuticsDetails" id="CollaborativeArrangementsAndLicensingAgreementsPtcTherapeuticsDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/CollaborativeArrangementsAndLicensingAgreementsBicycleTherapeuticsDetails" id="CollaborativeArrangementsAndLicensingAgreementsBicycleTherapeuticsDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/CollaborativeArrangementsAndLicensingAgreementsMetagenomiDetails" id="CollaborativeArrangementsAndLicensingAgreementsMetagenomiDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/CollaborativeArrangementsAndLicensingAgreementsAlnylamPharmaceuticalsIncDetails" id="CollaborativeArrangementsAndLicensingAgreementsAlnylamPharmaceuticalsIncDetails">
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        <link:definition>090430 - Disclosure - Collaborative Arrangements and Licensing Agreements, Alnylam Pharmaceuticals, Inc. (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" id="InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails">
        <!--Parent Role: Investments-->
        <link:definition>090500 - Disclosure - Investments, Contract Maturity of Available-for-Sale Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/InvestmentsSummaryOfInvestmentsDetails" id="InvestmentsSummaryOfInvestmentsDetails">
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        <link:definition>090502 - Disclosure - Investments, Summary of Investments (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionis.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails" id="InvestmentsInvestmentsTemporarilyImpairedDetails">
        <!--Parent Role: Investments-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionis.com/role/InvestmentsSummaryOfInvestmentsDetailsCalc2" id="InvestmentsSummaryOfInvestmentsDetailsCalc2">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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  <link:definitionLink xlink:type="extended" xlink:role="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" />
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.LAB
<SEQUENCE>11
<FILENAME>ions-20241231_lab.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by Broadridge PROfile 25.1.1.5279 Broadridge-->
<link:linkbase xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrli="http://www.xbrl.org/2003/instance">
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  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedPeriodStartLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedPeriodStartLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedLabel" />
  <link:labelLink xlink:type="extended" xlink:role="http://www.xbrl.org/2003/role/link">
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    <link:label xlink:type="resource" xlink:label="ecd_Rule10b51ArrAdoptedFlag_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_Rule10b51ArrAdoptedFlag_lbl1" xml:lang="en-US" id="ecd_Rule10b51ArrAdoptedFlag_lbl1">Rule 10b5-1 Arrangement Adopted [Flag]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_NonRule10b51ArrAdoptedFlag" xlink:label="NonRule10b51ArrAdoptedFlag" xlink:title="NonRule10b51ArrAdoptedFlag" />
    <link:label xlink:type="resource" xlink:label="ecd_NonRule10b51ArrAdoptedFlag" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_NonRule10b51ArrAdoptedFlag" xml:lang="en-US" id="ecd_NonRule10b51ArrAdoptedFlag">Non-Rule 10b5-1 Arrangement Adopted</link:label>
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    <link:label xlink:type="resource" xlink:label="ecd_NonRule10b51ArrAdoptedFlag_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_NonRule10b51ArrAdoptedFlag_lbl1" xml:lang="en-US" id="ecd_NonRule10b51ArrAdoptedFlag_lbl1">Non-Rule 10b5-1 Arrangement Adopted [Flag]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_MtrlTermsOfTrdArrTextBlock" xlink:label="MtrlTermsOfTrdArrTextBlock" xlink:title="MtrlTermsOfTrdArrTextBlock" />
    <link:label xlink:type="resource" xlink:label="ecd_MtrlTermsOfTrdArrTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_MtrlTermsOfTrdArrTextBlock" xml:lang="en-US" id="ecd_MtrlTermsOfTrdArrTextBlock">Material Terms of Trading Arrangement</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrIndName" xlink:label="TrdArrIndName" xlink:title="TrdArrIndName" />
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    <link:label xlink:type="resource" xlink:label="ecd_TrdArrIndName_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_TrdArrIndName_lbl1" xml:lang="en-US" id="ecd_TrdArrIndName_lbl1">Trading Arrangement, Individual Name</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrIndTitle" xlink:label="TrdArrIndTitle" xlink:title="TrdArrIndTitle" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrAdoptionDate" xlink:label="TrdArrAdoptionDate" xlink:title="TrdArrAdoptionDate" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrExpirationDate" xlink:label="TrdArrExpirationDate" xlink:title="TrdArrExpirationDate" />
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    <link:label xlink:type="resource" xlink:label="ecd_TrdArrExpirationDate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_TrdArrExpirationDate_lbl1" xml:lang="en-US" id="ecd_TrdArrExpirationDate_lbl1">Trading Arrangement Expiration Date</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrDuration" xlink:label="TrdArrDuration" xlink:title="TrdArrDuration" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrSecuritiesAggAvailAmt" xlink:label="TrdArrSecuritiesAggAvailAmt" xlink:title="TrdArrSecuritiesAggAvailAmt" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AmortizationOfIntangibleAssets" xlink:label="AmortizationOfIntangibleAssets" xlink:title="AmortizationOfIntangibleAssets" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfFinancialPositionAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfFinancialPositionAbstract" xml:lang="en-US" id="us-gaap_StatementOfFinancialPositionAbstract">CONSOLIDATED BALANCE SHEETS [Abstract]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesIssued" xlink:to="us-gaap_CommonStockSharesIssued" xlink:title="label: CommonStockSharesIssued to us-gaap_CommonStockSharesIssued" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesOutstanding1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_CommonStockSharesOutstanding1" xml:lang="en-US" id="us-gaap_CommonStockSharesOutstanding1">Common stock, shares outstanding (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesOutstanding" xlink:to="us-gaap_CommonStockSharesOutstanding1" xlink:title="label: CommonStockSharesOutstanding to us-gaap_CommonStockSharesOutstanding1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract" xml:lang="en-US" id="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract">Current [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl1" xml:lang="en-US" id="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl1">Current Income Tax Expense (Benefit), Continuing Operations [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract" xlink:to="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl1" xlink:title="label: CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract to us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract" xlink:label="DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract" xlink:title="DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="ComprehensiveIncomeNetOfTax" xlink:title="ComprehensiveIncomeNetOfTax" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskTypeDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskTypeDomain" xml:lang="en-US" id="us-gaap_ConcentrationRiskTypeDomain">Concentration Risk Type [Domain]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleDebtCurrent" xlink:label="ConvertibleDebtCurrent" xlink:title="ConvertibleDebtCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtCurrent" xml:lang="en-US" id="us-gaap_ConvertibleDebtCurrent">0.125 percent convertible senior notes, net</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditConcentrationRiskMember" xlink:label="CreditConcentrationRiskMember" xlink:title="CreditConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CreditConcentrationRiskMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CreditConcentrationRiskMember" xml:lang="en-US" id="us-gaap_CreditConcentrationRiskMember">Credit Concentration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CreditConcentrationRiskMember" xlink:to="us-gaap_CreditConcentrationRiskMember" xlink:title="label: CreditConcentrationRiskMember to us-gaap_CreditConcentrationRiskMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentFederalTaxExpenseBenefit" xlink:label="CurrentFederalTaxExpenseBenefit" xlink:title="CurrentFederalTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentFederalTaxExpenseBenefit" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CurrentFederalTaxExpenseBenefit" xml:lang="en-US" id="us-gaap_CurrentFederalTaxExpenseBenefit">Federal</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentFederalTaxExpenseBenefit" xlink:to="us-gaap_CurrentFederalTaxExpenseBenefit" xlink:title="label: CurrentFederalTaxExpenseBenefit to us-gaap_CurrentFederalTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentFederalTaxExpenseBenefit_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CurrentFederalTaxExpenseBenefit_lbl1" xml:lang="en-US" id="us-gaap_CurrentFederalTaxExpenseBenefit_lbl1">Current Federal Tax Expense (Benefit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentFederalTaxExpenseBenefit" xlink:to="us-gaap_CurrentFederalTaxExpenseBenefit_lbl1" xlink:title="label: CurrentFederalTaxExpenseBenefit to us-gaap_CurrentFederalTaxExpenseBenefit_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentForeignTaxExpenseBenefit" xlink:label="CurrentForeignTaxExpenseBenefit" xlink:title="CurrentForeignTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentForeignTaxExpenseBenefit" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CurrentForeignTaxExpenseBenefit" xml:lang="en-US" id="us-gaap_CurrentForeignTaxExpenseBenefit">Foreign</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentForeignTaxExpenseBenefit" xlink:to="us-gaap_CurrentForeignTaxExpenseBenefit" xlink:title="label: CurrentForeignTaxExpenseBenefit to us-gaap_CurrentForeignTaxExpenseBenefit" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentIncomeTaxExpenseBenefit" xlink:label="CurrentIncomeTaxExpenseBenefit" xlink:title="CurrentIncomeTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentIncomeTaxExpenseBenefit" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_CurrentIncomeTaxExpenseBenefit" xml:lang="en-US" id="us-gaap_CurrentIncomeTaxExpenseBenefit">Total current income tax expense (benefit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentIncomeTaxExpenseBenefit" xlink:to="us-gaap_CurrentIncomeTaxExpenseBenefit" xlink:title="label: CurrentIncomeTaxExpenseBenefit to us-gaap_CurrentIncomeTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl1" xml:lang="en-US" id="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl1">Current Income Tax Expense (Benefit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentIncomeTaxExpenseBenefit" xlink:to="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl1" xlink:title="label: CurrentIncomeTaxExpenseBenefit to us-gaap_CurrentIncomeTaxExpenseBenefit_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrent" xlink:label="LiabilitiesCurrent" xlink:title="LiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesCurrent" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent">Total current liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent_lbl1">Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent_lbl1" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrentAbstract" xlink:label="LiabilitiesCurrentAbstract" xlink:title="LiabilitiesCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrentAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesCurrentAbstract" xml:lang="en-US" id="us-gaap_LiabilitiesCurrentAbstract">Current liabilities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrentAbstract" xlink:title="label: LiabilitiesCurrentAbstract to us-gaap_LiabilitiesCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesCurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesCurrentAbstract_lbl1">Liabilities, Current [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrentAbstract_lbl1" xlink:title="label: LiabilitiesCurrentAbstract to us-gaap_LiabilitiesCurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentStateAndLocalTaxExpenseBenefit" xlink:label="CurrentStateAndLocalTaxExpenseBenefit" xlink:title="CurrentStateAndLocalTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentStateAndLocalTaxExpenseBenefit" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CurrentStateAndLocalTaxExpenseBenefit" xml:lang="en-US" id="us-gaap_CurrentStateAndLocalTaxExpenseBenefit">State</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentStateAndLocalTaxExpenseBenefit" xlink:to="us-gaap_CurrentStateAndLocalTaxExpenseBenefit" xlink:title="label: CurrentStateAndLocalTaxExpenseBenefit to us-gaap_CurrentStateAndLocalTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl1" xml:lang="en-US" id="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl1">Current State and Local Tax Expense (Benefit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentStateAndLocalTaxExpenseBenefit" xlink:to="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl1" xlink:title="label: CurrentStateAndLocalTaxExpenseBenefit to us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CustomerConcentrationRiskMember" xlink:label="CustomerConcentrationRiskMember" xlink:title="CustomerConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CustomerConcentrationRiskMember" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember">Strategic Partner [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CustomerConcentrationRiskMember" xlink:to="us-gaap_CustomerConcentrationRiskMember" xlink:title="label: CustomerConcentrationRiskMember to us-gaap_CustomerConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CustomerConcentrationRiskMember_lbl1" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember_lbl1">Customer Concentration Risk [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CustomerConcentrationRiskMember" xlink:to="us-gaap_CustomerConcentrationRiskMember_lbl1" xlink:title="label: CustomerConcentrationRiskMember to us-gaap_CustomerConcentrationRiskMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtDisclosureTextBlock" xlink:label="DebtDisclosureTextBlock" xlink:title="DebtDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtDisclosureTextBlock" xml:lang="en-US" id="us-gaap_DebtDisclosureTextBlock">Long-Term Obligations and Commitments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtDisclosureTextBlock" xlink:to="us-gaap_DebtDisclosureTextBlock" xlink:title="label: DebtDisclosureTextBlock to us-gaap_DebtDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_DebtDisclosureTextBlock_lbl1">Debt Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtDisclosureTextBlock" xlink:to="us-gaap_DebtDisclosureTextBlock_lbl1" xlink:title="label: DebtDisclosureTextBlock to us-gaap_DebtDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="DebtInstrumentCarryingAmount" xlink:title="DebtInstrumentCarryingAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentCarryingAmount" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentCarryingAmount" xml:lang="en-US" id="us-gaap_DebtInstrumentCarryingAmount">Outstanding principal balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentCarryingAmount" xlink:to="us-gaap_DebtInstrumentCarryingAmount" xlink:title="label: DebtInstrumentCarryingAmount to us-gaap_DebtInstrumentCarryingAmount" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="DebtInstrumentFaceAmount" xlink:title="DebtInstrumentFaceAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentFaceAmount" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount">Face amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentFaceAmount" xlink:to="us-gaap_DebtInstrumentFaceAmount" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_DebtInstrumentFaceAmount1" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount1">Face amount of offering</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentFaceAmount" xlink:to="us-gaap_DebtInstrumentFaceAmount1" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentFaceAmount_lbl2" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount_lbl2">Debt Instrument, Face Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentFaceAmount" xlink:to="us-gaap_DebtInstrumentFaceAmount_lbl2" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:label="DebtInstrumentInterestRateEffectivePercentage" xlink:title="DebtInstrumentInterestRateEffectivePercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentInterestRateEffectivePercentage" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateEffectivePercentage">Effective interest rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateEffectivePercentage" xlink:to="us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:title="label: DebtInstrumentInterestRateEffectivePercentage to us-gaap_DebtInstrumentInterestRateEffectivePercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1">Debt Instrument, Interest Rate, Effective Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateEffectivePercentage" xlink:to="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xlink:title="label: DebtInstrumentInterestRateEffectivePercentage to us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentInterestRateStatedPercentage" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateStatedPercentage">Interest rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateStatedPercentage" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:title="label: DebtInstrumentInterestRateStatedPercentage to us-gaap_DebtInstrumentInterestRateStatedPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentInterestRateStatedPercentage1" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateStatedPercentage1">Interest rate on convertible senior notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateStatedPercentage" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage1" xlink:title="label: DebtInstrumentInterestRateStatedPercentage to us-gaap_DebtInstrumentInterestRateStatedPercentage1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentMaturityDate" xlink:label="DebtInstrumentMaturityDate" xlink:title="DebtInstrumentMaturityDate" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentMaturityDate" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentMaturityDate" xml:lang="en-US" id="us-gaap_DebtInstrumentMaturityDate">Maturity date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentMaturityDate" xlink:to="us-gaap_DebtInstrumentMaturityDate" xlink:title="label: DebtInstrumentMaturityDate to us-gaap_DebtInstrumentMaturityDate" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentNameDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentNameDomain" xml:lang="en-US" id="us-gaap_DebtInstrumentNameDomain">Debt Instrument, Name [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNameDomain" xlink:to="us-gaap_DebtInstrumentNameDomain" xlink:title="label: DebtInstrumentNameDomain to us-gaap_DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentAxis" xml:lang="en-US" id="us-gaap_DebtInstrumentAxis">Debt Instrument [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentAxis" xlink:title="label: DebtInstrumentAxis to us-gaap_DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="DebtInstrumentLineItems" xlink:title="DebtInstrumentLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentLineItems" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentLineItems" xml:lang="en-US" id="us-gaap_DebtInstrumentLineItems">Debt Instrument [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentLineItems" xlink:title="label: DebtInstrumentLineItems to us-gaap_DebtInstrumentLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentTable" xlink:label="DebtInstrumentTable" xlink:title="DebtInstrumentTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentTable" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentTable" xml:lang="en-US" id="us-gaap_DebtInstrumentTable">Schedule of Long-term Debt Instruments [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentTable" xlink:to="us-gaap_DebtInstrumentTable" xlink:title="label: DebtInstrumentTable to us-gaap_DebtInstrumentTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsOfDebtIssuanceCosts" xlink:label="PaymentsOfDebtIssuanceCosts" xlink:title="PaymentsOfDebtIssuanceCosts" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredTaxLiabilitiesOther" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_DeferredTaxLiabilitiesOther" xml:lang="en-US" id="us-gaap_DeferredTaxLiabilitiesOther">Other</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredTaxLiabilitiesOther_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DeferredTaxLiabilitiesOther_lbl1" xml:lang="en-US" id="us-gaap_DeferredTaxLiabilitiesOther_lbl1">Deferred Tax Liabilities, Other</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxLiabilitiesOther" xlink:to="us-gaap_DeferredTaxLiabilitiesOther_lbl1" xlink:title="label: DeferredTaxLiabilitiesOther to us-gaap_DeferredTaxLiabilitiesOther_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DefinedContributionPlanCostRecognized" xlink:label="DefinedContributionPlanCostRecognized" xlink:title="DefinedContributionPlanCostRecognized" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DerivativesPolicyTextBlock" xlink:label="DerivativesPolicyTextBlock" xlink:title="DerivativesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DerivativesPolicyTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DerivativesPolicyTextBlock" xml:lang="en-US" id="us-gaap_DerivativesPolicyTextBlock">Call Spread</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_DerivativesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DerivativesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_DerivativesPolicyTextBlock_lbl1">Derivatives, Policy [Policy Text Block]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EarningsPerShareDiluted" xlink:label="EarningsPerShareDiluted" xlink:title="EarningsPerShareDiluted" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DomesticCountryMember" xlink:label="DomesticCountryMember" xlink:title="DomesticCountryMember" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:label="IncreaseDecreaseInOtherOperatingAssets" xlink:title="IncreaseDecreaseInOtherOperatingAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherOperatingAssets" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherOperatingAssets">Other current and long-term assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherOperatingAssets" xlink:to="us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:title="label: IncreaseDecreaseInOtherOperatingAssets to us-gaap_IncreaseDecreaseInOtherOperatingAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1">Increase (Decrease) in Other Operating Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherOperatingAssets" xlink:to="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xlink:title="label: IncreaseDecreaseInOtherOperatingAssets to us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestExpense" xlink:label="InterestExpense" xlink:title="InterestExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestExpense" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_InterestExpense" xml:lang="en-US" id="us-gaap_InterestExpense">Interest expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpense" xlink:to="us-gaap_InterestExpense" xlink:title="label: InterestExpense to us-gaap_InterestExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestExpense_lbl1" xml:lang="en-US" id="us-gaap_InterestExpense_lbl1">Interest Expense, Operating and Nonoperating</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpense" xlink:to="us-gaap_InterestExpense_lbl1" xlink:title="label: InterestExpense to us-gaap_InterestExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryFinishedGoods" xlink:label="InventoryFinishedGoods" xlink:title="InventoryFinishedGoods" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryFinishedGoods" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryFinishedGoods" xml:lang="en-US" id="us-gaap_InventoryFinishedGoods">Finished goods</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryFinishedGoods" xlink:to="us-gaap_InventoryFinishedGoods" xlink:title="label: InventoryFinishedGoods to us-gaap_InventoryFinishedGoods" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryFinishedGoods_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryFinishedGoods_lbl1" xml:lang="en-US" id="us-gaap_InventoryFinishedGoods_lbl1">Inventory, Finished Goods, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryFinishedGoods" xlink:to="us-gaap_InventoryFinishedGoods_lbl1" xlink:title="label: InventoryFinishedGoods to us-gaap_InventoryFinishedGoods_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryNet" xlink:label="InventoryNet" xlink:title="InventoryNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryNet" xml:lang="en-US" id="us-gaap_InventoryNet">Inventories</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet" xlink:title="label: InventoryNet to us-gaap_InventoryNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_InventoryNet1" xml:lang="en-US" id="us-gaap_InventoryNet1">Total inventories</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet1" xlink:title="label: InventoryNet to us-gaap_InventoryNet1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryNet_lbl2" xml:lang="en-US" id="us-gaap_InventoryNet_lbl2">Inventory, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet_lbl2" xlink:title="label: InventoryNet to us-gaap_InventoryNet_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryNetAbstract" xlink:label="InventoryNetAbstract" xlink:title="InventoryNetAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNetAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryNetAbstract" xml:lang="en-US" id="us-gaap_InventoryNetAbstract">Inventory [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNetAbstract" xlink:to="us-gaap_InventoryNetAbstract" xlink:title="label: InventoryNetAbstract to us-gaap_InventoryNetAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNetAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryNetAbstract_lbl1" xml:lang="en-US" id="us-gaap_InventoryNetAbstract_lbl1">Inventory, Net [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNetAbstract" xlink:to="us-gaap_InventoryNetAbstract_lbl1" xlink:title="label: InventoryNetAbstract to us-gaap_InventoryNetAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryRawMaterials" xlink:label="InventoryRawMaterials" xlink:title="InventoryRawMaterials" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryRawMaterials" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryRawMaterials" xml:lang="en-US" id="us-gaap_InventoryRawMaterials">Raw materials</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryRawMaterials" xlink:to="us-gaap_InventoryRawMaterials" xlink:title="label: InventoryRawMaterials to us-gaap_InventoryRawMaterials" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryRawMaterials_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryRawMaterials_lbl1" xml:lang="en-US" id="us-gaap_InventoryRawMaterials_lbl1">Inventory, Raw Materials, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryRawMaterials" xlink:to="us-gaap_InventoryRawMaterials_lbl1" xlink:title="label: InventoryRawMaterials to us-gaap_InventoryRawMaterials_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryWorkInProcess" xlink:label="InventoryWorkInProcess" xlink:title="InventoryWorkInProcess" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWorkInProcess" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryWorkInProcess" xml:lang="en-US" id="us-gaap_InventoryWorkInProcess">Work in process</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWorkInProcess" xlink:to="us-gaap_InventoryWorkInProcess" xlink:title="label: InventoryWorkInProcess to us-gaap_InventoryWorkInProcess" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWorkInProcess_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryWorkInProcess_lbl1" xml:lang="en-US" id="us-gaap_InventoryWorkInProcess_lbl1">Inventory, Work in Process, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWorkInProcess" xlink:to="us-gaap_InventoryWorkInProcess_lbl1" xlink:title="label: InventoryWorkInProcess to us-gaap_InventoryWorkInProcess_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryPolicyTextBlock" xlink:label="InventoryPolicyTextBlock" xlink:title="InventoryPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryPolicyTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryPolicyTextBlock" xml:lang="en-US" id="us-gaap_InventoryPolicyTextBlock">Inventories</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InventoryPolicyTextBlock_lbl1">Inventory, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InvestmentIncomeNet" xlink:label="InvestmentIncomeNet" xlink:title="InvestmentIncomeNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentIncomeNet" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet">Investment income</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentIncomeNet" xlink:to="us-gaap_InvestmentIncomeNet" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentIncomeNet_lbl1" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet_lbl1">Investment Income, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentIncomeNet" xlink:to="us-gaap_InvestmentIncomeNet_lbl1" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InvestmentPolicyTextBlock" xlink:label="InvestmentPolicyTextBlock" xlink:title="InvestmentPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentPolicyTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentPolicyTextBlock" xml:lang="en-US" id="us-gaap_InvestmentPolicyTextBlock">Cash, Cash Equivalents and Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentPolicyTextBlock" xlink:to="us-gaap_InvestmentPolicyTextBlock" xlink:title="label: InvestmentPolicyTextBlock to us-gaap_InvestmentPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentPolicyTextBlock_lbl1">Investment, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentPolicyTextBlock" xlink:to="us-gaap_InvestmentPolicyTextBlock_lbl1" xlink:title="label: InvestmentPolicyTextBlock to us-gaap_InvestmentPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsAbstract" xml:lang="en-US" id="us-gaap_InvestmentsAbstract">Investments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsAbstract" xlink:to="us-gaap_InvestmentsAbstract" xlink:title="label: InvestmentsAbstract to us-gaap_InvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LandImprovementsMember" xlink:label="LandImprovementsMember" xlink:title="LandImprovementsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LandImprovementsMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LandImprovementsMember" xml:lang="en-US" id="us-gaap_LandImprovementsMember">Land Improvements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LandImprovementsMember" xlink:to="us-gaap_LandImprovementsMember" xlink:title="label: LandImprovementsMember to us-gaap_LandImprovementsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LandImprovementsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LandImprovementsMember_lbl1" xml:lang="en-US" id="us-gaap_LandImprovementsMember_lbl1">Land Improvements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LandImprovementsMember" xlink:to="us-gaap_LandImprovementsMember_lbl1" xlink:title="label: LandImprovementsMember to us-gaap_LandImprovementsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LandMember" xlink:label="LandMember" xlink:title="LandMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LandMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LandMember" xml:lang="en-US" id="us-gaap_LandMember">Undeveloped Land in Carlsbad, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LandMember" xlink:to="us-gaap_LandMember" xlink:title="label: LandMember to us-gaap_LandMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LandMember1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LandMember1" xml:lang="en-US" id="us-gaap_LandMember1">Land [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LandMember" xlink:to="us-gaap_LandMember1" xlink:title="label: LandMember to us-gaap_LandMember1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LeaseholdImprovementsMember" xlink:label="LeaseholdImprovementsMember" xlink:title="LeaseholdImprovementsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LeaseholdImprovementsMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LeaseholdImprovementsMember" xml:lang="en-US" id="us-gaap_LeaseholdImprovementsMember">Leasehold Improvements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LeaseholdImprovementsMember" xlink:to="us-gaap_LeaseholdImprovementsMember" xlink:title="label: LeaseholdImprovementsMember to us-gaap_LeaseholdImprovementsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LeaseholdImprovementsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LeaseholdImprovementsMember_lbl1" xml:lang="en-US" id="us-gaap_LeaseholdImprovementsMember_lbl1">Leasehold Improvements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LeaseholdImprovementsMember" xlink:to="us-gaap_LeaseholdImprovementsMember_lbl1" xlink:title="label: LeaseholdImprovementsMember to us-gaap_LeaseholdImprovementsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Liabilities" xlink:label="Liabilities" xlink:title="Liabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_Liabilities" xml:lang="en-US" id="us-gaap_Liabilities">Total liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities" xlink:title="label: Liabilities to us-gaap_Liabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Liabilities_lbl1" xml:lang="en-US" id="us-gaap_Liabilities_lbl1">Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities_lbl1" xlink:title="label: Liabilities to us-gaap_Liabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="LiabilitiesAndStockholdersEquity" xlink:title="LiabilitiesAndStockholdersEquity" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquity" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquity">Total liabilities and stockholders' equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity" xlink:title="label: LiabilitiesAndStockholdersEquity to us-gaap_LiabilitiesAndStockholdersEquity" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquity_lbl1">Liabilities and Equity</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermLoansFromBank" xlink:label="LongTermLoansFromBank" xlink:title="LongTermLoansFromBank" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_LoansPayableToBank" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LoansPayableToBank" xml:lang="en-US" id="us-gaap_LoansPayableToBank">Mortgage debt</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LoansPayableToBank_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LoansPayableToBank_lbl1" xml:lang="en-US" id="us-gaap_LoansPayableToBank_lbl1">Loans Payable to Bank</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtCurrent" xlink:label="LongTermDebtCurrent" xlink:title="LongTermDebtCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtCurrent" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_LongTermDebtCurrent" xml:lang="en-US" id="us-gaap_LongTermDebtCurrent">Less: Current portion included in other current liabilities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtCurrent_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtCurrent_lbl1">Long-Term Debt, Current Maturities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive">Thereafter</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl1">Long-Term Debt, Maturity, after Year Five</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl1" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths">2025</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_lbl1">Long-Term Debt, Maturity, Year One</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive">2029</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl1">Long-Term Debt, Maturity, Year Five</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour">2028</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl1">Long-Term Debt, Maturity, Year Four</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl1" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree">2027</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl1">Long-Term Debt, Maturity, Year Three</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl1" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo">2026</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl1">Long-Term Debt, Maturity, Year Two</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl1" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtNoncurrent" xlink:label="LongTermDebtNoncurrent" xlink:title="LongTermDebtNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtNoncurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtNoncurrent" xml:lang="en-US" id="us-gaap_LongTermDebtNoncurrent">Total debt</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtNoncurrent_lbl1">Long-Term Debt, Excluding Current Maturities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtNoncurrent" xlink:to="us-gaap_LongTermDebtNoncurrent_lbl1" xlink:title="label: LongTermDebtNoncurrent to us-gaap_LongTermDebtNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebt" xlink:label="LongTermDebt" xlink:title="LongTermDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebt" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LongTermDebt" xml:lang="en-US" id="us-gaap_LongTermDebt">Total debt and mortgage maturities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebt_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebt_lbl1">Long-Term Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebt" xlink:to="us-gaap_LongTermDebt_lbl1" xlink:title="label: LongTermDebt to us-gaap_LongTermDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ManufacturingFacilityMember" xlink:label="ManufacturingFacilityMember" xlink:title="ManufacturingFacilityMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ManufacturingFacilityMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ManufacturingFacilityMember" xml:lang="en-US" id="us-gaap_ManufacturingFacilityMember">Manufacturing Facility [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_MaturitiesOfLongTermDebtAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MaturitiesOfLongTermDebtAbstract" xml:lang="en-US" id="us-gaap_MaturitiesOfLongTermDebtAbstract">Debt Maturities [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="NetCashProvidedByUsedInFinancingActivities" xlink:title="NetCashProvidedByUsedInFinancingActivities" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1">Net Cash Provided by (Used in) Financing Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xlink:title="label: NetCashProvidedByUsedInFinancingActivities to us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInFinancingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract">Financing activities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:title="label: NetCashProvidedByUsedInFinancingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1">Net Cash Provided by (Used in) Financing Activities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xlink:title="label: NetCashProvidedByUsedInFinancingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="NetCashProvidedByUsedInInvestingActivities" xlink:title="NetCashProvidedByUsedInInvestingActivities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivities" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivities">Net cash used in investing activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:title="label: NetCashProvidedByUsedInInvestingActivities to us-gaap_NetCashProvidedByUsedInInvestingActivities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1">Net Cash Provided by (Used in) Investing Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" xlink:title="label: NetCashProvidedByUsedInInvestingActivities to us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInInvestingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract">Investing activities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:title="label: NetCashProvidedByUsedInInvestingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1">Net Cash Provided by (Used in) Investing Activities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xlink:title="label: NetCashProvidedByUsedInInvestingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="NetCashProvidedByUsedInOperatingActivities" xlink:title="NetCashProvidedByUsedInOperatingActivities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivities" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivities">Net cash used in operating activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:title="label: NetCashProvidedByUsedInOperatingActivities to us-gaap_NetCashProvidedByUsedInOperatingActivities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1">Net Cash Provided by (Used in) Operating Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xlink:title="label: NetCashProvidedByUsedInOperatingActivities to us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract">Operating activities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="label: NetCashProvidedByUsedInOperatingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1">Net Cash Provided by (Used in) Operating Activities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xlink:title="label: NetCashProvidedByUsedInOperatingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetIncomeLoss" xml:lang="en-US" id="us-gaap_NetIncomeLoss">Net loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetIncomeLoss1" xml:lang="en-US" id="us-gaap_NetIncomeLoss1">Net loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss1" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetIncomeLoss_lbl2" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl2">Net Income (Loss)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl2" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="NonoperatingIncomeExpenseAbstract" xlink:title="NonoperatingIncomeExpenseAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NonoperatingIncomeExpenseAbstract" xml:lang="en-US" id="us-gaap_NonoperatingIncomeExpenseAbstract">Other income (expense):</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_NonoperatingIncomeExpenseAbstract" xlink:title="label: NonoperatingIncomeExpenseAbstract to us-gaap_NonoperatingIncomeExpenseAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xml:lang="en-US" id="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1">Nonoperating Income (Expense) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xlink:title="label: NonoperatingIncomeExpenseAbstract to us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLossCarryforwards" xlink:label="OperatingLossCarryforwards" xlink:title="OperatingLossCarryforwards" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLossCarryforwards" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLossCarryforwards" xml:lang="en-US" id="us-gaap_OperatingLossCarryforwards">Net operating loss carryforwards</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLossCarryforwards" xlink:to="us-gaap_OperatingLossCarryforwards" xlink:title="label: OperatingLossCarryforwards to us-gaap_OperatingLossCarryforwards" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLossCarryforwards_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLossCarryforwards_lbl1" xml:lang="en-US" id="us-gaap_OperatingLossCarryforwards_lbl1">Operating Loss Carryforwards</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLossCarryforwards" xlink:to="us-gaap_OperatingLossCarryforwards_lbl1" xlink:title="label: OperatingLossCarryforwards to us-gaap_OperatingLossCarryforwards_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingIncomeLoss" xlink:label="OperatingIncomeLoss" xlink:title="OperatingIncomeLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingIncomeLoss" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_OperatingIncomeLoss" xml:lang="en-US" id="us-gaap_OperatingIncomeLoss">Loss from operations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingIncomeLoss" xlink:to="us-gaap_OperatingIncomeLoss" xlink:title="label: OperatingIncomeLoss to us-gaap_OperatingIncomeLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingIncomeLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingIncomeLoss_lbl1" xml:lang="en-US" id="us-gaap_OperatingIncomeLoss_lbl1">Operating Income (Loss)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingIncomeLoss" xlink:to="us-gaap_OperatingIncomeLoss_lbl1" xlink:title="label: OperatingIncomeLoss to us-gaap_OperatingIncomeLoss_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Revenues" xlink:label="Revenues" xlink:title="Revenues" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Revenues" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_Revenues" xml:lang="en-US" id="us-gaap_Revenues">Revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Revenues" xlink:to="us-gaap_Revenues" xlink:title="label: Revenues to us-gaap_Revenues" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Revenues_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Revenues_lbl1" xml:lang="en-US" id="us-gaap_Revenues_lbl1">Revenues</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Revenues" xlink:to="us-gaap_Revenues_lbl1" xlink:title="label: Revenues to us-gaap_Revenues_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAssetsCurrent" xlink:label="OtherAssetsCurrent" xlink:title="OtherAssetsCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherAssetsCurrent" xml:lang="en-US" id="us-gaap_OtherAssetsCurrent">Other current assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAssetsCurrent" xlink:to="us-gaap_OtherAssetsCurrent" xlink:title="label: OtherAssetsCurrent to us-gaap_OtherAssetsCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherAssetsCurrent_lbl1" xml:lang="en-US" id="us-gaap_OtherAssetsCurrent_lbl1">Other Assets, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAssetsCurrent" xlink:to="us-gaap_OtherAssetsCurrent_lbl1" xlink:title="label: OtherAssetsCurrent to us-gaap_OtherAssetsCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherLiabilities" xlink:label="OtherLiabilities" xlink:title="OtherLiabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherLiabilities" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherLiabilities" xml:lang="en-US" id="us-gaap_OtherLiabilities">Other obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherLiabilities" xlink:to="us-gaap_OtherLiabilities" xlink:title="label: OtherLiabilities to us-gaap_OtherLiabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherLiabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherLiabilities_lbl1" xml:lang="en-US" id="us-gaap_OtherLiabilities_lbl1">Other Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherLiabilities" xlink:to="us-gaap_OtherLiabilities_lbl1" xlink:title="label: OtherLiabilities to us-gaap_OtherLiabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="OtherNonoperatingIncomeExpense" xlink:title="OtherNonoperatingIncomeExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNonoperatingIncomeExpense" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherNonoperatingIncomeExpense" xml:lang="en-US" id="us-gaap_OtherNonoperatingIncomeExpense">Other income (expense)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherNonoperatingIncomeExpense" xlink:to="us-gaap_OtherNonoperatingIncomeExpense" xlink:title="label: OtherNonoperatingIncomeExpense to us-gaap_OtherNonoperatingIncomeExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNonoperatingIncomeExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherNonoperatingIncomeExpense_lbl1" xml:lang="en-US" id="us-gaap_OtherNonoperatingIncomeExpense_lbl1">Other Nonoperating Income (Expense)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherNonoperatingIncomeExpense" xlink:to="us-gaap_OtherNonoperatingIncomeExpense_lbl1" xlink:title="label: OtherNonoperatingIncomeExpense to us-gaap_OtherNonoperatingIncomeExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:label="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:title="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfWarrants" xlink:label="ProceedsFromIssuanceOfWarrants" xlink:title="ProceedsFromIssuanceOfWarrants" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ReconciliationOfUnrecognizedTaxBenefitsExcludingAmountsPertainingToExaminedTaxReturnsRollForward" xlink:label="ReconciliationOfUnrecognizedTaxBenefitsExcludingAmountsPertainingToExaminedTaxReturnsRollForward" xlink:title="ReconciliationOfUnrecognizedTaxBenefitsExcludingAmountsPertainingToExaminedTaxReturnsRollForward" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems">Share-based Compensation Arrangement by Share-based Payment Award [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xml:lang="en-US" id="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable">Schedule of Share-based Compensation Arrangements by Share-based Payment Award [Table]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShortTermInvestments" xlink:to="us-gaap_ShortTermInvestments_lbl1" xlink:title="label: ShortTermInvestments to us-gaap_ShortTermInvestments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StateAndLocalJurisdictionMember" xlink:label="StateAndLocalJurisdictionMember" xlink:title="StateAndLocalJurisdictionMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StateAndLocalJurisdictionMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StateAndLocalJurisdictionMember" xml:lang="en-US" id="us-gaap_StateAndLocalJurisdictionMember">State [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StateAndLocalJurisdictionMember" xlink:to="us-gaap_StateAndLocalJurisdictionMember" xlink:title="label: StateAndLocalJurisdictionMember to us-gaap_StateAndLocalJurisdictionMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StateAndLocalJurisdictionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StateAndLocalJurisdictionMember_lbl1" xml:lang="en-US" id="us-gaap_StateAndLocalJurisdictionMember_lbl1">State and Local Jurisdiction [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StateAndLocalJurisdictionMember" xlink:to="us-gaap_StateAndLocalJurisdictionMember_lbl1" xlink:title="label: StateAndLocalJurisdictionMember to us-gaap_StateAndLocalJurisdictionMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementOfCashFlowsAbstract" xlink:label="StatementOfCashFlowsAbstract" xlink:title="StatementOfCashFlowsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfCashFlowsAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfCashFlowsAbstract" xml:lang="en-US" id="us-gaap_StatementOfCashFlowsAbstract">CONSOLIDATED STATEMENTS OF CASH FLOWS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfCashFlowsAbstract" xlink:to="us-gaap_StatementOfCashFlowsAbstract" xlink:title="label: StatementOfCashFlowsAbstract to us-gaap_StatementOfCashFlowsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:label="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:title="StatementOfIncomeAndComprehensiveIncomeAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xml:lang="en-US" id="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract">CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:title="label: StatementOfIncomeAndComprehensiveIncomeAbstract to us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfStockholdersEquityAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfStockholdersEquityAbstract" xml:lang="en-US" id="us-gaap_StatementOfStockholdersEquityAbstract">CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfStockholdersEquityAbstract" xlink:to="us-gaap_StatementOfStockholdersEquityAbstract" xlink:title="label: StatementOfStockholdersEquityAbstract to us-gaap_StatementOfStockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:label="ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:title="ShareBasedCompensationOptionAndIncentivePlansPolicy" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:to="us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:title="label: ShareBasedCompensationOptionAndIncentivePlansPolicy to us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockOptionMember" xlink:label="StockOptionMember" xlink:title="StockOptionMember" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ClassOfStockDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ClassOfStockDomain" xml:lang="en-US" id="us-gaap_ClassOfStockDomain">Class of Stock [Domain]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_SelectedQuarterlyFinancialInformationAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SelectedQuarterlyFinancialInformationAbstract" xml:lang="en-US" id="us-gaap_SelectedQuarterlyFinancialInformationAbstract">Fourth Quarter Financial Data (Unaudited) [Abstract]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SelectedQuarterlyFinancialInformationAbstract" xlink:to="us-gaap_SelectedQuarterlyFinancialInformationAbstract_lbl1" xlink:title="label: SelectedQuarterlyFinancialInformationAbstract to us-gaap_SelectedQuarterlyFinancialInformationAbstract_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xlink:title="label: PaymentsToAcquireAvailableForSaleSecuritiesDebt to us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsMember" xlink:label="CashAndCashEquivalentsMember" xlink:title="CashAndCashEquivalentsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashAndCashEquivalentsMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashAndCashEquivalentsMember" xml:lang="en-US" id="us-gaap_CashAndCashEquivalentsMember">Cash and Cash Equivalents [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashAndCashEquivalentsMember" xlink:to="us-gaap_CashAndCashEquivalentsMember" xlink:title="label: CashAndCashEquivalentsMember to us-gaap_CashAndCashEquivalentsMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InternalRevenueServiceIRSMember" xlink:label="InternalRevenueServiceIRSMember" xlink:title="InternalRevenueServiceIRSMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InternalRevenueServiceIRSMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InternalRevenueServiceIRSMember" xml:lang="en-US" id="us-gaap_InternalRevenueServiceIRSMember">Federal [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InternalRevenueServiceIRSMember" xlink:to="us-gaap_InternalRevenueServiceIRSMember" xlink:title="label: InternalRevenueServiceIRSMember to us-gaap_InternalRevenueServiceIRSMember" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:title="label: IncreaseDecreaseInStockholdersEquityRollForward to us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xlink:title="label: IncreaseDecreaseInStockholdersEquityRollForward to us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredFinanceCostsNet" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_DeferredFinanceCostsNet" xml:lang="en-US" id="us-gaap_DeferredFinanceCostsNet">Less: Debt issuance costs</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredFinanceCostsNet1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DeferredFinanceCostsNet1" xml:lang="en-US" id="us-gaap_DeferredFinanceCostsNet1">Unamortized debt issuance costs</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredFinanceCostsNet_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DeferredFinanceCostsNet_lbl2" xml:lang="en-US" id="us-gaap_DeferredFinanceCostsNet_lbl2">Debt Issuance Costs, Net</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleDebtNoncurrent" xlink:label="ConvertibleDebtNoncurrent" xlink:title="ConvertibleDebtNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtNoncurrent" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent">Convertible senior notes, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent_lbl1">Convertible Debt, Noncurrent</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleDebt" xlink:label="ConvertibleDebt" xlink:title="ConvertibleDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebt" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebt" xml:lang="en-US" id="us-gaap_ConvertibleDebt">Convertible senior notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebt" xlink:to="us-gaap_ConvertibleDebt" xlink:title="label: ConvertibleDebt to us-gaap_ConvertibleDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebt_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebt_lbl1">Convertible Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebt" xlink:to="us-gaap_ConvertibleDebt_lbl1" xlink:title="label: ConvertibleDebt to us-gaap_ConvertibleDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="OtherAssetsNoncurrent" xlink:title="OtherAssetsNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsNoncurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherAssetsNoncurrent" xml:lang="en-US" id="us-gaap_OtherAssetsNoncurrent">Deposits and other assets</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherAssetsNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_OtherAssetsNoncurrent_lbl1">Other Assets, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAssetsNoncurrent" xlink:to="us-gaap_OtherAssetsNoncurrent_lbl1" xlink:title="label: OtherAssetsNoncurrent to us-gaap_OtherAssetsNoncurrent_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerShareBasicAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EarningsPerShareBasicAbstract" xml:lang="en-US" id="us-gaap_EarningsPerShareBasicAbstract">Basic and Diluted Net Loss Per Share [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EarningsPerShareBasicAbstract" xlink:to="us-gaap_EarningsPerShareBasicAbstract" xlink:title="label: EarningsPerShareBasicAbstract to us-gaap_EarningsPerShareBasicAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerShareBasicAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EarningsPerShareBasicAbstract_lbl1" xml:lang="en-US" id="us-gaap_EarningsPerShareBasicAbstract_lbl1">Earnings Per Share, Basic [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:label="ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:title="ScheduleOfAvailableForSaleSecuritiesLineItems" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance" xlink:label="IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance" xlink:title="IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountsReceivableMember" xlink:to="us-gaap_AccountsReceivableMember_lbl1" xlink:title="label: AccountsReceivableMember to us-gaap_AccountsReceivableMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="StatementEquityComponentsAxis" xlink:title="StatementEquityComponentsAxis" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:label="AdditionalPaidInCapitalMember" xlink:title="AdditionalPaidInCapitalMember" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetainedEarningsMember" xlink:label="RetainedEarningsMember" xlink:title="RetainedEarningsMember" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsMember" xlink:to="us-gaap_RetainedEarningsMember_lbl1" xlink:title="label: RetainedEarningsMember to us-gaap_RetainedEarningsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:label="AccumulatedOtherComprehensiveIncomeMember" xlink:title="AccumulatedOtherComprehensiveIncomeMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccumulatedOtherComprehensiveIncomeMember" xml:lang="en-US" id="us-gaap_AccumulatedOtherComprehensiveIncomeMember">Accumulated Other Comprehensive Loss [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccumulatedOtherComprehensiveIncomeMember" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:title="label: AccumulatedOtherComprehensiveIncomeMember to us-gaap_AccumulatedOtherComprehensiveIncomeMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityComponentDomain" xlink:label="EquityComponentDomain" xlink:title="EquityComponentDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquityComponentDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquityComponentDomain" xml:lang="en-US" id="us-gaap_EquityComponentDomain">Equity Component [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityComponentDomain" xlink:to="us-gaap_EquityComponentDomain" xlink:title="label: EquityComponentDomain to us-gaap_EquityComponentDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="EmployeeStockOptionMember" xlink:title="EmployeeStockOptionMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeStockOptionMember" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember">Employee Stock Options [Member]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember1" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl2" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RealizedInvestmentGainsLosses" xlink:label="RealizedInvestmentGainsLosses" xlink:title="RealizedInvestmentGainsLosses" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RealizedInvestmentGainsLosses" xlink:to="us-gaap_RealizedInvestmentGainsLosses_lbl1" xlink:title="label: RealizedInvestmentGainsLosses to us-gaap_RealizedInvestmentGainsLosses_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="StockIssuedDuringPeriodValueNewIssues" xlink:title="StockIssuedDuringPeriodValueNewIssues" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="StockIssuedDuringPeriodSharesNewIssues" xlink:title="StockIssuedDuringPeriodSharesNewIssues" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesNewIssues" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesNewIssues">Issuance of public common stock, net (in shares)</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" xlink:to="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans to us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementBusinessSegmentsAxis" xlink:label="StatementBusinessSegmentsAxis" xlink:title="StatementBusinessSegmentsAxis" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl1">Costs and Expenses [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl2" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:label="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:title="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharesIssued" xlink:label="SharesIssued" xlink:title="SharesIssued" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ClassOfStockLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ClassOfStockLineItems_lbl1" xml:lang="en-US" id="us-gaap_ClassOfStockLineItems_lbl1">Class of Stock [Line Items]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfStockByClassTable" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfStockByClassTable" xml:lang="en-US" id="us-gaap_ScheduleOfStockByClassTable">Schedule of Stock by Class [Table]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xml:lang="en-US" id="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract">Adjustments to reconcile net loss to net cash used in operating activities:</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:label="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:title="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xml:lang="en-US" id="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:title="label: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1">Convertible Notes Payable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xlink:title="label: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtCurrentAndNoncurrentAbstract" xlink:label="LongtermDebtCurrentAndNoncurrentAbstract" xlink:title="LongtermDebtCurrentAndNoncurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract" xml:lang="en-US" id="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract">Long-Term Obligations [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongtermDebtCurrentAndNoncurrentAbstract" xlink:to="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract" xlink:title="label: LongtermDebtCurrentAndNoncurrentAbstract to us-gaap_LongtermDebtCurrentAndNoncurrentAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestPayableCurrentAndNoncurrent" xlink:label="InterestPayableCurrentAndNoncurrent" xlink:title="InterestPayableCurrentAndNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPayableCurrentAndNoncurrent" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_InterestPayableCurrentAndNoncurrent" xml:lang="en-US" id="us-gaap_InterestPayableCurrentAndNoncurrent">Less: Fixed and determinable interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPayableCurrentAndNoncurrent" xlink:to="us-gaap_InterestPayableCurrentAndNoncurrent" xlink:title="label: InterestPayableCurrentAndNoncurrent to us-gaap_InterestPayableCurrentAndNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPayableCurrentAndNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestPayableCurrentAndNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_InterestPayableCurrentAndNoncurrent_lbl1">Interest Payable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPayableCurrentAndNoncurrent" xlink:to="us-gaap_InterestPayableCurrentAndNoncurrent_lbl1" xlink:title="label: InterestPayableCurrentAndNoncurrent to us-gaap_InterestPayableCurrentAndNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsPayableCurrent" xlink:label="AccountsPayableCurrent" xlink:title="AccountsPayableCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccountsPayableCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccountsPayableCurrent" xml:lang="en-US" id="us-gaap_AccountsPayableCurrent">Accounts payable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountsPayableCurrent" xlink:to="us-gaap_AccountsPayableCurrent" xlink:title="label: AccountsPayableCurrent to us-gaap_AccountsPayableCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccountsPayableCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccountsPayableCurrent_lbl1" xml:lang="en-US" id="us-gaap_AccountsPayableCurrent_lbl1">Accounts Payable, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountsPayableCurrent" xlink:to="us-gaap_AccountsPayableCurrent_lbl1" xlink:title="label: AccountsPayableCurrent to us-gaap_AccountsPayableCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="AccruedLiabilitiesCurrent" xlink:title="AccruedLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedLiabilitiesCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccruedLiabilitiesCurrent" xml:lang="en-US" id="us-gaap_AccruedLiabilitiesCurrent">Accrued liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedLiabilitiesCurrent" xlink:title="label: AccruedLiabilitiesCurrent to us-gaap_AccruedLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedLiabilitiesCurrent1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_AccruedLiabilitiesCurrent1" xml:lang="en-US" id="us-gaap_AccruedLiabilitiesCurrent1">Total accrued liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedLiabilitiesCurrent1" xlink:title="label: AccruedLiabilitiesCurrent to us-gaap_AccruedLiabilitiesCurrent1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedLiabilitiesCurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccruedLiabilitiesCurrent_lbl2" xml:lang="en-US" id="us-gaap_AccruedLiabilitiesCurrent_lbl2">Accrued Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedLiabilitiesCurrent_lbl2" xlink:title="label: AccruedLiabilitiesCurrent to us-gaap_AccruedLiabilitiesCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="EmployeeRelatedLiabilitiesCurrent" xlink:title="EmployeeRelatedLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeRelatedLiabilitiesCurrent" xml:lang="en-US" id="us-gaap_EmployeeRelatedLiabilitiesCurrent">Accrued compensation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeRelatedLiabilitiesCurrent" xlink:to="us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:title="label: EmployeeRelatedLiabilitiesCurrent to us-gaap_EmployeeRelatedLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1">Employee-related Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeRelatedLiabilitiesCurrent" xlink:to="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" xlink:title="label: EmployeeRelatedLiabilitiesCurrent to us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAccruedLiabilitiesCurrent" xlink:label="OtherAccruedLiabilitiesCurrent" xlink:title="OtherAccruedLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAccruedLiabilitiesCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherAccruedLiabilitiesCurrent" xml:lang="en-US" id="us-gaap_OtherAccruedLiabilitiesCurrent">Other miscellaneous expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAccruedLiabilitiesCurrent" xlink:to="us-gaap_OtherAccruedLiabilitiesCurrent" xlink:title="label: OtherAccruedLiabilitiesCurrent to us-gaap_OtherAccruedLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAccruedLiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherAccruedLiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_OtherAccruedLiabilitiesCurrent_lbl1">Other Accrued Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAccruedLiabilitiesCurrent" xlink:to="us-gaap_OtherAccruedLiabilitiesCurrent_lbl1" xlink:title="label: OtherAccruedLiabilitiesCurrent to us-gaap_OtherAccruedLiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccruedLiabilitiesCurrentAbstract" xlink:label="AccruedLiabilitiesCurrentAbstract" xlink:title="AccruedLiabilitiesCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedLiabilitiesCurrentAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccruedLiabilitiesCurrentAbstract" xml:lang="en-US" id="us-gaap_AccruedLiabilitiesCurrentAbstract">Accrued Liabilities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesCurrentAbstract" xlink:to="us-gaap_AccruedLiabilitiesCurrentAbstract" xlink:title="label: AccruedLiabilitiesCurrentAbstract to us-gaap_AccruedLiabilitiesCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedLiabilitiesCurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccruedLiabilitiesCurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_AccruedLiabilitiesCurrentAbstract_lbl1">Accrued Liabilities, Current [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesCurrentAbstract" xlink:to="us-gaap_AccruedLiabilitiesCurrentAbstract_lbl1" xlink:title="label: AccruedLiabilitiesCurrentAbstract to us-gaap_AccruedLiabilitiesCurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:label="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:title="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xml:lang="en-US" id="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent">Unrealized gains (losses) on investments, net of tax</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:label="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:title="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ImpairmentOfIntangibleAssetsFinitelived" xlink:label="ImpairmentOfIntangibleAssetsFinitelived" xlink:title="ImpairmentOfIntangibleAssetsFinitelived" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ImpairmentOfIntangibleAssetsFinitelived" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ImpairmentOfIntangibleAssetsFinitelived" xml:lang="en-US" id="us-gaap_ImpairmentOfIntangibleAssetsFinitelived">Non-cash losses related to other assets</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameAxis" xlink:label="PlanNameAxis" xlink:title="PlanNameAxis" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:label="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:title="NewAccountingPronouncementsPolicyPolicyTextBlock" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskCreditRisk" xlink:label="ConcentrationRiskCreditRisk" xlink:title="ConcentrationRiskCreditRisk" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets" xlink:label="DeferredTaxAssetsGoodwillAndIntangibleAssets" xlink:title="DeferredTaxAssetsGoodwillAndIntangibleAssets" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife" xlink:label="PropertyPlantAndEquipmentUsefulLife" xlink:title="PropertyPlantAndEquipmentUsefulLife" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1 to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1">Vesting period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1 to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Award Vesting Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1 to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1">Weighted average period for recognition</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1 to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition2" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition2">Weighted average period for recognition</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition2" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1 to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition2" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl2" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl2">Share-Based Payment Arrangement, Nonvested Award, Cost Not yet Recognized, Period for Recognition</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl2" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1 to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent">Percentage of fair market value used to determine purchase price of stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Purchase Price of Common Stock, Percent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NumberOfOperatingSegments" xlink:label="NumberOfOperatingSegments" xlink:title="NumberOfOperatingSegments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NumberOfOperatingSegments" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NumberOfOperatingSegments" xml:lang="en-US" id="us-gaap_NumberOfOperatingSegments">Number of operating segments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfOperatingSegments" xlink:to="us-gaap_NumberOfOperatingSegments" xlink:title="label: NumberOfOperatingSegments to us-gaap_NumberOfOperatingSegments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NumberOfOperatingSegments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NumberOfOperatingSegments_lbl1" xml:lang="en-US" id="us-gaap_NumberOfOperatingSegments_lbl1">Number of Operating Segments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfOperatingSegments" xlink:to="us-gaap_NumberOfOperatingSegments_lbl1" xlink:title="label: NumberOfOperatingSegments to us-gaap_NumberOfOperatingSegments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherCurrentAssetsMember" xlink:label="OtherCurrentAssetsMember" xlink:title="OtherCurrentAssetsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherCurrentAssetsMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherCurrentAssetsMember" xml:lang="en-US" id="us-gaap_OtherCurrentAssetsMember">Other Current Assets [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCurrentAssetsMember" xlink:to="us-gaap_OtherCurrentAssetsMember" xlink:title="label: OtherCurrentAssetsMember to us-gaap_OtherCurrentAssetsMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:label="SellingGeneralAndAdministrativeExpensesMember" xlink:title="SellingGeneralAndAdministrativeExpensesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpensesMember" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpensesMember">Selling, General and Administrative [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpensesMember" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:title="label: SellingGeneralAndAdministrativeExpensesMember to us-gaap_SellingGeneralAndAdministrativeExpensesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1">Selling, General and Administrative Expenses [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpensesMember" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xlink:title="label: SellingGeneralAndAdministrativeExpensesMember to us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" xlink:label="ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" xlink:title="ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" xml:lang="en-US" id="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock">Gross Unrecognized Tax Benefits</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" xlink:to="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" xlink:title="label: ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock to us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl1">Schedule of Unrecognized Tax Benefits Roll Forward [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" xlink:to="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl1" xlink:title="label: ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock to us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="ConcentrationRiskPercentage1" xlink:title="ConcentrationRiskPercentage1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskPercentage1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskPercentage1" xml:lang="en-US" id="us-gaap_ConcentrationRiskPercentage1">Concentration percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskPercentage1" xlink:to="us-gaap_ConcentrationRiskPercentage1" xlink:title="label: ConcentrationRiskPercentage1 to us-gaap_ConcentrationRiskPercentage1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:label="DebtInstrumentConvertibleConversionPrice1" xlink:title="DebtInstrumentConvertibleConversionPrice1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentConvertibleConversionPrice1" xml:lang="en-US" id="us-gaap_DebtInstrumentConvertibleConversionPrice1">Conversion price per share (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPrice1" xlink:to="us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:title="label: DebtInstrumentConvertibleConversionPrice1 to us-gaap_DebtInstrumentConvertibleConversionPrice1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="BalanceSheetLocationDomain" xlink:title="BalanceSheetLocationDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_BalanceSheetLocationDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_BalanceSheetLocationDomain" xml:lang="en-US" id="us-gaap_BalanceSheetLocationDomain">Balance Sheet Location [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BalanceSheetLocationDomain" xlink:to="us-gaap_BalanceSheetLocationDomain" xlink:title="label: BalanceSheetLocationDomain to us-gaap_BalanceSheetLocationDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfSalesMember" xlink:label="CostOfSalesMember" xlink:title="CostOfSalesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfSalesMember" xml:lang="en-US" id="us-gaap_CostOfSalesMember">Cost of Sales [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesMember_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesMember_lbl1">Cost of Sales [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember_lbl1" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InvestmentTextBlock" xlink:label="InvestmentTextBlock" xlink:title="InvestmentTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentTextBlock" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentTextBlock" xml:lang="en-US" id="us-gaap_InvestmentTextBlock">Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentTextBlock" xlink:to="us-gaap_InvestmentTextBlock" xlink:title="label: InvestmentTextBlock to us-gaap_InvestmentTextBlock" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" xlink:label="DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" xlink:title="DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" xml:lang="en-US" id="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount">Employee contribution limit per calendar year</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" xlink:to="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" xlink:title="label: DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount to us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl1" xml:lang="en-US" id="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl1">Defined Contribution Plan, Maximum Annual Contributions Per Employee, Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" xlink:to="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl1" xlink:title="label: DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount to us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueNetAssetLiabilityAbstract" xlink:label="FairValueNetAssetLiabilityAbstract" xlink:title="FairValueNetAssetLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueNetAssetLiabilityAbstract" xml:lang="en-US" id="us-gaap_FairValueNetAssetLiabilityAbstract">Fair Value Measurements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_FairValueNetAssetLiabilityAbstract" xlink:title="label: FairValueNetAssetLiabilityAbstract to us-gaap_FairValueNetAssetLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1">Fair Value, Net Asset (Liability) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xlink:title="label: FairValueNetAssetLiabilityAbstract to us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock" xml:lang="en-US" id="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock">Liability Related to Sale of Future Royalties</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1">Other Noncurrent Liabilities [Table Text Block]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNonoperatingIncomeExpenseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherNonoperatingIncomeExpenseMember_lbl1" xml:lang="en-US" id="us-gaap_OtherNonoperatingIncomeExpenseMember_lbl1">Other Nonoperating Income (Expense) [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAwardTrancheOneMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationAwardTrancheOneMember" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAwardTrancheOneMember">One Year from Date of Grant [Member]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAwardTrancheTwoMember" xlink:to="us-gaap_ShareBasedCompensationAwardTrancheTwoMember" xlink:title="label: ShareBasedCompensationAwardTrancheTwoMember to us-gaap_ShareBasedCompensationAwardTrancheTwoMember" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAwardTrancheThreeMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationAwardTrancheThreeMember" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAwardTrancheThreeMember">Three-Year Period [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAwardTrancheThreeMember" xlink:to="us-gaap_ShareBasedCompensationAwardTrancheThreeMember" xlink:title="label: ShareBasedCompensationAwardTrancheThreeMember to us-gaap_ShareBasedCompensationAwardTrancheThreeMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxAuthorityNameAxis" xlink:label="IncomeTaxAuthorityNameAxis" xlink:title="IncomeTaxAuthorityNameAxis" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxAuthorityNameDomain" xlink:label="IncomeTaxAuthorityNameDomain" xlink:title="IncomeTaxAuthorityNameDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxAuthorityNameDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeTaxAuthorityNameDomain" xml:lang="en-US" id="us-gaap_IncomeTaxAuthorityNameDomain">Income Tax Authority, Name [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxAuthorityNameDomain" xlink:to="us-gaap_IncomeTaxAuthorityNameDomain" xlink:title="label: IncomeTaxAuthorityNameDomain to us-gaap_IncomeTaxAuthorityNameDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CaliforniaFranchiseTaxBoardMember" xlink:label="CaliforniaFranchiseTaxBoardMember" xlink:title="CaliforniaFranchiseTaxBoardMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CaliforniaFranchiseTaxBoardMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CaliforniaFranchiseTaxBoardMember" xml:lang="en-US" id="us-gaap_CaliforniaFranchiseTaxBoardMember">California [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_CaliforniaFranchiseTaxBoardMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CaliforniaFranchiseTaxBoardMember_lbl1" xml:lang="en-US" id="us-gaap_CaliforniaFranchiseTaxBoardMember_lbl1">California Franchise Tax Board [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CaliforniaFranchiseTaxBoardMember" xlink:to="us-gaap_CaliforniaFranchiseTaxBoardMember_lbl1" xlink:title="label: CaliforniaFranchiseTaxBoardMember to us-gaap_CaliforniaFranchiseTaxBoardMember_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_DefinedContributionPlanTable" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DefinedContributionPlanTable" xml:lang="en-US" id="us-gaap_DefinedContributionPlanTable">Defined Contribution Plan [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DefinedContributionPlanTable" xlink:to="us-gaap_DefinedContributionPlanTable" xlink:title="label: DefinedContributionPlanTable to us-gaap_DefinedContributionPlanTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DefinedContributionPlanDisclosureLineItems" xlink:label="DefinedContributionPlanDisclosureLineItems" xlink:title="DefinedContributionPlanDisclosureLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DefinedContributionPlanDisclosureLineItems" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DefinedContributionPlanDisclosureLineItems" xml:lang="en-US" id="us-gaap_DefinedContributionPlanDisclosureLineItems">Defined Contribution Plan Disclosure [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DefinedContributionPlanDisclosureLineItems" xlink:to="us-gaap_DefinedContributionPlanDisclosureLineItems" xlink:title="label: DefinedContributionPlanDisclosureLineItems to us-gaap_DefinedContributionPlanDisclosureLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:label="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:title="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract">Available-for-sale Debt Securities [Abstract]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl1" xlink:title="label: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueTableTextBlock" xlink:label="DisaggregationOfRevenueTableTextBlock" xlink:title="DisaggregationOfRevenueTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DisaggregationOfRevenueTableTextBlock" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueTableTextBlock">Revenues</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized" xlink:label="ContractWithCustomerLiabilityRevenueRecognized" xlink:title="ContractWithCustomerLiabilityRevenueRecognized" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerAbstract" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerAbstract">Revenues [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerAbstract" xlink:title="label: RevenueFromContractWithCustomerAbstract to us-gaap_RevenueFromContractWithCustomerAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerAbstract1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerAbstract1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerAbstract1">Revenue:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerAbstract1" xlink:title="label: RevenueFromContractWithCustomerAbstract to us-gaap_RevenueFromContractWithCustomerAbstract1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerTextBlock" xlink:label="RevenueFromContractWithCustomerTextBlock" xlink:title="RevenueFromContractWithCustomerTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerTextBlock" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerTextBlock">Revenues</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTextBlock" xlink:to="us-gaap_RevenueFromContractWithCustomerTextBlock" xlink:title="label: RevenueFromContractWithCustomerTextBlock to us-gaap_RevenueFromContractWithCustomerTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl1">Revenue from Contract with Customer [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTextBlock" xlink:to="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl1" xlink:title="label: RevenueFromContractWithCustomerTextBlock to us-gaap_RevenueFromContractWithCustomerTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeDisclosureAbstract" xlink:label="LesseeDisclosureAbstract" xlink:title="LesseeDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeDisclosureAbstract" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_LesseeDisclosureAbstract" xml:lang="en-US" id="us-gaap_LesseeDisclosureAbstract">Operating Leases [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeDisclosureAbstract" xlink:to="us-gaap_LesseeDisclosureAbstract" xlink:title="label: LesseeDisclosureAbstract to us-gaap_LesseeDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeDisclosureAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeDisclosureAbstract_lbl1" xml:lang="en-US" id="us-gaap_LesseeDisclosureAbstract_lbl1">Lessee Disclosure [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeDisclosureAbstract" xlink:to="us-gaap_LesseeDisclosureAbstract_lbl1" xlink:title="label: LesseeDisclosureAbstract to us-gaap_LesseeDisclosureAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityAbstract" xlink:label="ContractWithCustomerLiabilityAbstract" xlink:title="ContractWithCustomerLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityAbstract" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityAbstract">Deferred Revenue [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityAbstract" xlink:title="label: ContractWithCustomerLiabilityAbstract to us-gaap_ContractWithCustomerLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1">Contract with Customer, Liability [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xlink:title="label: ContractWithCustomerLiabilityAbstract to us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="ContractWithCustomerLiabilityCurrent" xlink:title="ContractWithCustomerLiabilityCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent">Current portion of deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1">Contract with Customer, Liability, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="ContractWithCustomerLiabilityNoncurrent" xlink:title="ContractWithCustomerLiabilityNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityNoncurrent" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityNoncurrent">Long-term deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityNoncurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:title="label: ContractWithCustomerLiabilityNoncurrent to us-gaap_ContractWithCustomerLiabilityNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1">Contract with Customer, Liability, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityNoncurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xlink:title="label: ContractWithCustomerLiabilityNoncurrent to us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiability" xlink:label="ContractWithCustomerLiability" xlink:title="ContractWithCustomerLiability" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiability" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability">Deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiability_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl1">Contract with Customer, Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability_lbl1" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="OperatingLeaseRightOfUseAsset" xlink:title="OperatingLeaseRightOfUseAsset" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseRightOfUseAsset" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAsset">Right-of-use assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAsset" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset" xlink:title="label: OperatingLeaseRightOfUseAsset to us-gaap_OperatingLeaseRightOfUseAsset" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseRightOfUseAsset1" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAsset1">Right-of-use operating lease assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAsset" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset1" xlink:title="label: OperatingLeaseRightOfUseAsset to us-gaap_OperatingLeaseRightOfUseAsset1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:label="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:title="OperatingLeaseLiabilitiesPaymentsDueAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract">Future Payments for Operating Lease Liabilities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:title="label: OperatingLeaseLiabilitiesPaymentsDueAbstract to us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1">Lessee, Operating Lease, Liability, to be Paid, Fiscal Year Maturity [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" xlink:title="label: OperatingLeaseLiabilitiesPaymentsDueAbstract to us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">Revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="label: RevenueFromContractWithCustomerExcludingAssessedTax to us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1">Revenue from Contract with Customer, Excluding Assessed Tax</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xlink:title="label: RevenueFromContractWithCustomerExcludingAssessedTax to us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerMember" xlink:label="RevenueFromContractWithCustomerMember" xlink:title="RevenueFromContractWithCustomerMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerMember" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerMember" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerMember">Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerMember" xlink:to="us-gaap_RevenueFromContractWithCustomerMember" xlink:title="label: RevenueFromContractWithCustomerMember to us-gaap_RevenueFromContractWithCustomerMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerMember_lbl1">Revenue from Contract with Customer Benchmark [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerMember" xlink:to="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xlink:title="label: RevenueFromContractWithCustomerMember to us-gaap_RevenueFromContractWithCustomerMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeLeaseDescriptionTable" xlink:label="LesseeLeaseDescriptionTable" xlink:title="LesseeLeaseDescriptionTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeaseDescriptionTable" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeaseDescriptionTable" xml:lang="en-US" id="us-gaap_LesseeLeaseDescriptionTable">Lessee, Lease, Description [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeaseDescriptionTable" xlink:to="us-gaap_LesseeLeaseDescriptionTable" xlink:title="label: LesseeLeaseDescriptionTable to us-gaap_LesseeLeaseDescriptionTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeLeaseDescriptionLineItems" xlink:label="LesseeLeaseDescriptionLineItems" xlink:title="LesseeLeaseDescriptionLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeaseDescriptionLineItems" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeaseDescriptionLineItems" xml:lang="en-US" id="us-gaap_LesseeLeaseDescriptionLineItems">Lessee, Lease, Description [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="us-gaap_LesseeLeaseDescriptionLineItems" xlink:title="label: LesseeLeaseDescriptionLineItems to us-gaap_LesseeLeaseDescriptionLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:label="EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:title="EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xml:lang="en-US" id="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations">Effects of exchange rates on cash</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:to="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:title="label: EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations to us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations_lbl1" xml:lang="en-US" id="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations_lbl1">Effect of Exchange Rate on Cash, Cash Equivalents, Restricted Cash, and Restricted Cash Equivalents, Including Disposal Group and Discontinued Operations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:to="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations_lbl1" xlink:title="label: EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations to us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:label="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:title="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent" xlink:label="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:title="OperatingLeaseWeightedAverageDiscountRatePercent" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour">2028</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearFour to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearThree to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearTwo to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock">Future Payments for Operating Lease Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityMaturityTableTextBlock" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock" xlink:title="label: LesseeOperatingLeaseLiabilityMaturityTableTextBlock to us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityMaturityTableTextBlock" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityMaturityTableTextBlock to us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseExpense" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseExpense" xml:lang="en-US" id="us-gaap_OperatingLeaseExpense">Rent expense</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LessorOperatingLeasePaymentsToBeReceived" xlink:label="LessorOperatingLeasePaymentsToBeReceived" xlink:title="LessorOperatingLeasePaymentsToBeReceived" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeasePaymentsToBeReceived" xlink:to="us-gaap_LessorOperatingLeasePaymentsToBeReceived" xlink:title="label: LessorOperatingLeasePaymentsToBeReceived to us-gaap_LessorOperatingLeasePaymentsToBeReceived" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleAndLeasebackTransactionGainLossNet" xlink:label="SaleAndLeasebackTransactionGainLossNet" xlink:title="SaleAndLeasebackTransactionGainLossNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SaleAndLeasebackTransactionGainLossNet" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_SaleAndLeasebackTransactionGainLossNet" xml:lang="en-US" id="us-gaap_SaleAndLeasebackTransactionGainLossNet">Loss (gain) on sale of real estate assets</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SaleAndLeasebackTransactionGainLossNet" xlink:to="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl1" xlink:title="label: SaleAndLeasebackTransactionGainLossNet to us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiability" xlink:label="OperatingLeaseLiability" xlink:title="OperatingLeaseLiability" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiability1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiability1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiability1">Lease liabilities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiability_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiability_lbl2" xml:lang="en-US" id="us-gaap_OperatingLeaseLiability_lbl2">Operating Lease, Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiability" xlink:to="us-gaap_OperatingLeaseLiability_lbl2" xlink:title="label: OperatingLeaseLiability to us-gaap_OperatingLeaseLiability_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="OperatingLeaseLiabilityCurrent" xlink:title="OperatingLeaseLiabilityCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_OperatingLeaseLiabilityCurrent" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityCurrent">Less: Current portion (included in other current liabilities)</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiabilityCurrent_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityCurrent_lbl1">Operating Lease, Liability, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilityCurrent" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent_lbl1" xlink:title="label: OperatingLeaseLiabilityCurrent to us-gaap_OperatingLeaseLiabilityCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:label="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:title="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount">Less: Imputed interest</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityUndiscountedExcessAmount to us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:label="OperatingLeaseLiabilityNoncurrent" xlink:title="OperatingLeaseLiabilityNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiabilityNoncurrent" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityNoncurrent">Long-term lease liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilityNoncurrent" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:title="label: OperatingLeaseLiabilityNoncurrent to us-gaap_OperatingLeaseLiabilityNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiabilityNoncurrent1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityNoncurrent1">Total long-term lease liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilityNoncurrent" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent1" xlink:title="label: OperatingLeaseLiabilityNoncurrent to us-gaap_OperatingLeaseLiabilityNoncurrent1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList" xlink:label="OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList" xlink:title="OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList" xlink:to="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList" xlink:title="label: OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList to us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl1">Operating Lease, Liability, Current, Statement of Financial Position [Extensible Enumeration]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeLeasesPolicyTextBlock" xlink:label="LesseeLeasesPolicyTextBlock" xlink:title="LesseeLeasesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeasesPolicyTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeLeasesPolicyTextBlock" xml:lang="en-US" id="us-gaap_LesseeLeasesPolicyTextBlock">Leases</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeasesTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeasesTextBlock" xml:lang="en-US" id="us-gaap_LesseeOperatingLeasesTextBlock">Long-Term Obligations and Commitments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasesTextBlock" xlink:to="us-gaap_LesseeOperatingLeasesTextBlock" xlink:title="label: LesseeOperatingLeasesTextBlock to us-gaap_LesseeOperatingLeasesTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeasesTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeasesTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeasesTextBlock_lbl1">Lessee, Operating Leases [Text Block]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:label="OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:title="OperatingLeaseWeightedAverageRemainingLeaseTerm1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1" xml:lang="en-US" id="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1">Weighted average remaining lease term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:to="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:title="label: OperatingLeaseWeightedAverageRemainingLeaseTerm1 to us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl1">Operating Lease, Weighted Average Remaining Lease Term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:to="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl1" xlink:title="label: OperatingLeaseWeightedAverageRemainingLeaseTerm1 to us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseTermOfContract" xlink:label="LesseeOperatingLeaseTermOfContract" xlink:title="LesseeOperatingLeaseTermOfContract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseTermOfContract" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_LesseeOperatingLeaseTermOfContract" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseTermOfContract">Initial term of lease</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GranteeStatusAxis" xlink:label="GranteeStatusAxis" xlink:title="GranteeStatusAxis" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedPaymentArrangementEmployeeMember" xlink:label="ShareBasedPaymentArrangementEmployeeMember" xlink:title="ShareBasedPaymentArrangementEmployeeMember" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration" xlink:to="us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration" xlink:title="label: ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration to us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent" xlink:label="EffectiveIncomeTaxRateReconciliationFdiiPercent" xlink:title="EffectiveIncomeTaxRateReconciliationFdiiPercent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent">Foreign-derived intangible income benefit</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationFdiiPercent" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent" xlink:title="label: EffectiveIncomeTaxRateReconciliationFdiiPercent to us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl1" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl1">Effective Income Tax Rate Reconciliation, FDII, Percent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationFdiiPercent" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl1" xlink:title="label: EffectiveIncomeTaxRateReconciliationFdiiPercent to us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount" xlink:label="EffectiveIncomeTaxRateReconciliationFdiiAmount" xlink:title="EffectiveIncomeTaxRateReconciliationFdiiAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount">Foreign-derived intangible income benefit</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationFdiiAmount" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount" xlink:title="label: EffectiveIncomeTaxRateReconciliationFdiiAmount to us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl1" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl1">Effective Income Tax Rate Reconciliation, FDII, Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationFdiiAmount" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl1" xlink:title="label: EffectiveIncomeTaxRateReconciliationFdiiAmount to us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentReportingOtherItemCompositionDescription" xlink:label="SegmentReportingOtherItemCompositionDescription" xlink:title="SegmentReportingOtherItemCompositionDescription" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingOtherItemCompositionDescription" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SegmentReportingOtherItemCompositionDescription" xml:lang="en-US" id="us-gaap_SegmentReportingOtherItemCompositionDescription">Segment Reporting, Other Segment Item, Composition, Description</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingOtherItemCompositionDescription" xlink:to="us-gaap_SegmentReportingOtherItemCompositionDescription" xlink:title="label: SegmentReportingOtherItemCompositionDescription to us-gaap_SegmentReportingOtherItemCompositionDescription" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentReportingOtherItemAmount" xlink:label="SegmentReportingOtherItemAmount" xlink:title="SegmentReportingOtherItemAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingOtherItemAmount" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SegmentReportingOtherItemAmount" xml:lang="en-US" id="us-gaap_SegmentReportingOtherItemAmount">Other segment items</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingOtherItemAmount" xlink:to="us-gaap_SegmentReportingOtherItemAmount" xlink:title="label: SegmentReportingOtherItemAmount to us-gaap_SegmentReportingOtherItemAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingOtherItemAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SegmentReportingOtherItemAmount_lbl1" xml:lang="en-US" id="us-gaap_SegmentReportingOtherItemAmount_lbl1">Segment Reporting, Other Segment Item, Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingOtherItemAmount" xlink:to="us-gaap_SegmentReportingOtherItemAmount_lbl1" xlink:title="label: SegmentReportingOtherItemAmount to us-gaap_SegmentReportingOtherItemAmount_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain" xlink:title="NameOfMajorCustomerDomain" />
    <link:label xlink:type="resource" xlink:label="srt_NameOfMajorCustomerDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_NameOfMajorCustomerDomain" xml:lang="en-US" id="srt_NameOfMajorCustomerDomain">Customer [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NameOfMajorCustomerDomain" xlink:to="srt_NameOfMajorCustomerDomain" xlink:title="label: NameOfMajorCustomerDomain to srt_NameOfMajorCustomerDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ExecutiveOfficerMember" xlink:label="ExecutiveOfficerMember" xlink:title="ExecutiveOfficerMember" />
    <link:label xlink:type="resource" xlink:label="srt_ExecutiveOfficerMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="srt_ExecutiveOfficerMember" xml:lang="en-US" id="srt_ExecutiveOfficerMember">Executive Officers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ExecutiveOfficerMember" xlink:to="srt_ExecutiveOfficerMember" xlink:title="label: ExecutiveOfficerMember to srt_ExecutiveOfficerMember" />
    <link:label xlink:type="resource" xlink:label="srt_ExecutiveOfficerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ExecutiveOfficerMember_lbl1" xml:lang="en-US" id="srt_ExecutiveOfficerMember_lbl1">Executive Officer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ExecutiveOfficerMember" xlink:to="srt_ExecutiveOfficerMember_lbl1" xlink:title="label: ExecutiveOfficerMember to srt_ExecutiveOfficerMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MajorCustomersAxis" xlink:label="MajorCustomersAxis" xlink:title="MajorCustomersAxis" />
    <link:label xlink:type="resource" xlink:label="srt_MajorCustomersAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MajorCustomersAxis" xml:lang="en-US" id="srt_MajorCustomersAxis">Customer [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MajorCustomersAxis" xlink:to="srt_MajorCustomersAxis" xlink:title="label: MajorCustomersAxis to srt_MajorCustomersAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:label xlink:type="resource" xlink:label="srt_RangeAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeAxis" xml:lang="en-US" id="srt_RangeAxis">Statistical Measurement [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeAxis" xlink:to="srt_RangeAxis" xlink:title="label: RangeAxis to srt_RangeAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:label xlink:type="resource" xlink:label="srt_RangeMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeMember" xml:lang="en-US" id="srt_RangeMember">Statistical Measurement [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeMember" xlink:to="srt_RangeMember" xlink:title="label: RangeMember to srt_RangeMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MaximumMember" xlink:label="MaximumMember" xlink:title="MaximumMember" />
    <link:label xlink:type="resource" xlink:label="srt_MaximumMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MaximumMember" xml:lang="en-US" id="srt_MaximumMember">Maximum [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumMember" xlink:to="srt_MaximumMember" xlink:title="label: MaximumMember to srt_MaximumMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MinimumMember" xlink:label="MinimumMember" xlink:title="MinimumMember" />
    <link:label xlink:type="resource" xlink:label="srt_MinimumMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MinimumMember" xml:lang="en-US" id="srt_MinimumMember">Minimum [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinimumMember" xlink:to="srt_MinimumMember" xlink:title="label: MinimumMember to srt_MinimumMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock" xlink:label="ContractualObligationFiscalYearMaturityScheduleTableTextBlock" xlink:title="ContractualObligationFiscalYearMaturityScheduleTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock" xml:lang="en-US" id="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock">Debt Maturity Schedules</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligationFiscalYearMaturityScheduleTableTextBlock" xlink:to="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock" xlink:title="label: ContractualObligationFiscalYearMaturityScheduleTableTextBlock to srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligationFiscalYearMaturityScheduleTableTextBlock" xlink:to="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl1" xlink:title="label: ContractualObligationFiscalYearMaturityScheduleTableTextBlock to srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl1" />
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    <link:label xlink:type="resource" xlink:label="srt_ProductsAndServicesDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductsAndServicesDomain" xml:lang="en-US" id="srt_ProductsAndServicesDomain">Product and Service [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductsAndServicesDomain" xlink:to="srt_ProductsAndServicesDomain" xlink:title="label: ProductsAndServicesDomain to srt_ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ProductOrServiceAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductOrServiceAxis" xml:lang="en-US" id="srt_ProductOrServiceAxis">Product and Service [Axis]</link:label>
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    <link:label xlink:type="resource" xlink:label="dei_EntityTaxIdentificationNumber" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityTaxIdentificationNumber" xml:lang="en-US" id="dei_EntityTaxIdentificationNumber">Entity Tax Identification Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityTaxIdentificationNumber" xlink:to="dei_EntityTaxIdentificationNumber" xlink:title="label: EntityTaxIdentificationNumber to dei_EntityTaxIdentificationNumber" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityIncorporationStateCountryCode" xlink:label="EntityIncorporationStateCountryCode" xlink:title="EntityIncorporationStateCountryCode" />
    <link:label xlink:type="resource" xlink:label="dei_EntityIncorporationStateCountryCode" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityIncorporationStateCountryCode" xml:lang="en-US" id="dei_EntityIncorporationStateCountryCode">Entity Incorporation, State or Country Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityIncorporationStateCountryCode" xlink:to="dei_EntityIncorporationStateCountryCode" xlink:title="label: EntityIncorporationStateCountryCode to dei_EntityIncorporationStateCountryCode" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_CurrentFiscalYearEndDate" xlink:label="CurrentFiscalYearEndDate" xlink:title="CurrentFiscalYearEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_CurrentFiscalYearEndDate" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CurrentFiscalYearEndDate" xml:lang="en-US" id="dei_CurrentFiscalYearEndDate">Current Fiscal Year End Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentFiscalYearEndDate" xlink:to="dei_CurrentFiscalYearEndDate" xlink:title="label: CurrentFiscalYearEndDate to dei_CurrentFiscalYearEndDate" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityWellKnownSeasonedIssuer" xlink:label="EntityWellKnownSeasonedIssuer" xlink:title="EntityWellKnownSeasonedIssuer" />
    <link:label xlink:type="resource" xlink:label="dei_EntityWellKnownSeasonedIssuer" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityWellKnownSeasonedIssuer" xml:lang="en-US" id="dei_EntityWellKnownSeasonedIssuer">Entity Well-known Seasoned Issuer</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityWellKnownSeasonedIssuer" xlink:to="dei_EntityWellKnownSeasonedIssuer" xlink:title="label: EntityWellKnownSeasonedIssuer to dei_EntityWellKnownSeasonedIssuer" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityVoluntaryFilers" xlink:label="EntityVoluntaryFilers" xlink:title="EntityVoluntaryFilers" />
    <link:label xlink:type="resource" xlink:label="dei_EntityVoluntaryFilers" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityVoluntaryFilers" xml:lang="en-US" id="dei_EntityVoluntaryFilers">Entity Voluntary Filers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityVoluntaryFilers" xlink:to="dei_EntityVoluntaryFilers" xlink:title="label: EntityVoluntaryFilers to dei_EntityVoluntaryFilers" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityCurrentReportingStatus" xlink:label="EntityCurrentReportingStatus" xlink:title="EntityCurrentReportingStatus" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCurrentReportingStatus" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCurrentReportingStatus" xml:lang="en-US" id="dei_EntityCurrentReportingStatus">Entity Current Reporting Status</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCurrentReportingStatus" xlink:to="dei_EntityCurrentReportingStatus" xlink:title="label: EntityCurrentReportingStatus to dei_EntityCurrentReportingStatus" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityShellCompany" xlink:label="EntityShellCompany" xlink:title="EntityShellCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityShellCompany" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityShellCompany" xml:lang="en-US" id="dei_EntityShellCompany">Entity Shell Company</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityShellCompany" xlink:to="dei_EntityShellCompany" xlink:title="label: EntityShellCompany to dei_EntityShellCompany" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityFilerCategory" xlink:label="EntityFilerCategory" xlink:title="EntityFilerCategory" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFilerCategory" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFilerCategory" xml:lang="en-US" id="dei_EntityFilerCategory">Entity Filer Category</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityFilerCategory" xlink:to="dei_EntityFilerCategory" xlink:title="label: EntityFilerCategory to dei_EntityFilerCategory" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntitySmallBusiness" xlink:label="EntitySmallBusiness" xlink:title="EntitySmallBusiness" />
    <link:label xlink:type="resource" xlink:label="dei_EntitySmallBusiness" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntitySmallBusiness" xml:lang="en-US" id="dei_EntitySmallBusiness">Entity Small Business</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntitySmallBusiness" xlink:to="dei_EntitySmallBusiness" xlink:title="label: EntitySmallBusiness to dei_EntitySmallBusiness" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityEmergingGrowthCompany" xlink:label="EntityEmergingGrowthCompany" xlink:title="EntityEmergingGrowthCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityEmergingGrowthCompany" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityEmergingGrowthCompany" xml:lang="en-US" id="dei_EntityEmergingGrowthCompany">Entity Emerging Growth Company</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityEmergingGrowthCompany" xlink:to="dei_EntityEmergingGrowthCompany" xlink:title="label: EntityEmergingGrowthCompany to dei_EntityEmergingGrowthCompany" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityPublicFloat" xlink:label="EntityPublicFloat" xlink:title="EntityPublicFloat" />
    <link:label xlink:type="resource" xlink:label="dei_EntityPublicFloat" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityPublicFloat" xml:lang="en-US" id="dei_EntityPublicFloat">Entity Public Float</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityPublicFloat" xlink:to="dei_EntityPublicFloat" xlink:title="label: EntityPublicFloat to dei_EntityPublicFloat" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityAddressAddressLine1" xlink:label="EntityAddressAddressLine1" xlink:title="EntityAddressAddressLine1" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressAddressLine1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressAddressLine1" xml:lang="en-US" id="dei_EntityAddressAddressLine1">Entity Address, Address Line One</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressAddressLine1" xlink:to="dei_EntityAddressAddressLine1" xlink:title="label: EntityAddressAddressLine1 to dei_EntityAddressAddressLine1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityAddressCityOrTown" xlink:label="EntityAddressCityOrTown" xlink:title="EntityAddressCityOrTown" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressCityOrTown" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressCityOrTown" xml:lang="en-US" id="dei_EntityAddressCityOrTown">Entity Address, City or Town</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressCityOrTown" xlink:to="dei_EntityAddressCityOrTown" xlink:title="label: EntityAddressCityOrTown to dei_EntityAddressCityOrTown" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityAddressStateOrProvince" xlink:label="EntityAddressStateOrProvince" xlink:title="EntityAddressStateOrProvince" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressStateOrProvince" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressStateOrProvince" xml:lang="en-US" id="dei_EntityAddressStateOrProvince">Entity Address, State or Province</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressStateOrProvince" xlink:to="dei_EntityAddressStateOrProvince" xlink:title="label: EntityAddressStateOrProvince to dei_EntityAddressStateOrProvince" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityAddressPostalZipCode" xlink:label="EntityAddressPostalZipCode" xlink:title="EntityAddressPostalZipCode" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressPostalZipCode" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressPostalZipCode" xml:lang="en-US" id="dei_EntityAddressPostalZipCode">Entity Address, Postal Zip Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressPostalZipCode" xlink:to="dei_EntityAddressPostalZipCode" xlink:title="label: EntityAddressPostalZipCode to dei_EntityAddressPostalZipCode" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_CityAreaCode" xlink:label="CityAreaCode" xlink:title="CityAreaCode" />
    <link:label xlink:type="resource" xlink:label="dei_CityAreaCode" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CityAreaCode" xml:lang="en-US" id="dei_CityAreaCode">City Area Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CityAreaCode" xlink:to="dei_CityAreaCode" xlink:title="label: CityAreaCode to dei_CityAreaCode" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_LocalPhoneNumber" xlink:label="LocalPhoneNumber" xlink:title="LocalPhoneNumber" />
    <link:label xlink:type="resource" xlink:label="dei_LocalPhoneNumber" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_LocalPhoneNumber" xml:lang="en-US" id="dei_LocalPhoneNumber">Local Phone Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LocalPhoneNumber" xlink:to="dei_LocalPhoneNumber" xlink:title="label: LocalPhoneNumber to dei_LocalPhoneNumber" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_Security12bTitle" xlink:label="Security12bTitle" xlink:title="Security12bTitle" />
    <link:label xlink:type="resource" xlink:label="dei_Security12bTitle" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_Security12bTitle" xml:lang="en-US" id="dei_Security12bTitle">Title of 12(b) Security</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Security12bTitle" xlink:to="dei_Security12bTitle" xlink:title="label: Security12bTitle to dei_Security12bTitle" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_TradingSymbol" xlink:label="TradingSymbol" xlink:title="TradingSymbol" />
    <link:label xlink:type="resource" xlink:label="dei_TradingSymbol" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_TradingSymbol" xml:lang="en-US" id="dei_TradingSymbol">Trading Symbol</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TradingSymbol" xlink:to="dei_TradingSymbol" xlink:title="label: TradingSymbol to dei_TradingSymbol" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_SecurityExchangeName" xlink:label="SecurityExchangeName" xlink:title="SecurityExchangeName" />
    <link:label xlink:type="resource" xlink:label="dei_SecurityExchangeName" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_SecurityExchangeName" xml:lang="en-US" id="dei_SecurityExchangeName">Security Exchange Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecurityExchangeName" xlink:to="dei_SecurityExchangeName" xlink:title="label: SecurityExchangeName to dei_SecurityExchangeName" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityCommonStockSharesOutstanding" xlink:label="EntityCommonStockSharesOutstanding" xlink:title="EntityCommonStockSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCommonStockSharesOutstanding" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCommonStockSharesOutstanding" xml:lang="en-US" id="dei_EntityCommonStockSharesOutstanding">Entity Common Stock, Shares Outstanding</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCommonStockSharesOutstanding" xlink:to="dei_EntityCommonStockSharesOutstanding" xlink:title="label: EntityCommonStockSharesOutstanding to dei_EntityCommonStockSharesOutstanding" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_AuditorName" xlink:label="AuditorName" xlink:title="AuditorName" />
    <link:label xlink:type="resource" xlink:label="dei_AuditorName" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AuditorName" xml:lang="en-US" id="dei_AuditorName">Auditor Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AuditorName" xlink:to="dei_AuditorName" xlink:title="label: AuditorName to dei_AuditorName" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_AuditorFirmId" xlink:label="AuditorFirmId" xlink:title="AuditorFirmId" />
    <link:label xlink:type="resource" xlink:label="dei_AuditorFirmId" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AuditorFirmId" xml:lang="en-US" id="dei_AuditorFirmId">Auditor Firm ID</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AuditorFirmId" xlink:to="dei_AuditorFirmId" xlink:title="label: AuditorFirmId to dei_AuditorFirmId" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_AuditorLocation" xlink:label="AuditorLocation" xlink:title="AuditorLocation" />
    <link:label xlink:type="resource" xlink:label="dei_AuditorLocation" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AuditorLocation" xml:lang="en-US" id="dei_AuditorLocation">Auditor Location</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AuditorLocation" xlink:to="dei_AuditorLocation" xlink:title="label: AuditorLocation to dei_AuditorLocation" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1">Collaborative Arrangements and Licensing Agreements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsAbstract to ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ConvertibleSeniorNotes175PercentMember" xlink:label="ConvertibleSeniorNotes175PercentMember" xlink:title="ConvertibleSeniorNotes175PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes175PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentMember_lbl">1.75 percent convertible senior notes due June 2028.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes175PercentMember" xlink:to="ions_ConvertibleSeniorNotes175PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes175PercentMember to ions_ConvertibleSeniorNotes175PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes175PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentMember_lbl1">Convertible Senior Notes 1.75 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes175PercentMember" xlink:to="ions_ConvertibleSeniorNotes175PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes175PercentMember to ions_ConvertibleSeniorNotes175PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentMember" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes175PercentMember" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentMember">1.75% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes175PercentMember" xlink:to="ions_ConvertibleSeniorNotes175PercentMember" xlink:title="label: ConvertibleSeniorNotes175PercentMember to ions_ConvertibleSeniorNotes175PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes175PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentMember_lbl2">1.75 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes175PercentMember" xlink:to="ions_ConvertibleSeniorNotes175PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes175PercentMember to ions_ConvertibleSeniorNotes175PercentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LongTermObligationsCurrent" xlink:label="LongTermObligationsCurrent" xlink:title="LongTermObligationsCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermObligationsCurrent_lbl" xml:lang="en-US" id="ions_LongTermObligationsCurrent_lbl">Amount of long-term debt, lease obligations and other obligations., classified as current.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsCurrent" xlink:to="ions_LongTermObligationsCurrent_lbl" xlink:title="label: LongTermObligationsCurrent to ions_LongTermObligationsCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligationsCurrent_lbl1" xml:lang="en-US" id="ions_LongTermObligationsCurrent_lbl1">Long-term Obligations, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsCurrent" xlink:to="ions_LongTermObligationsCurrent_lbl1" xlink:title="label: LongTermObligationsCurrent to ions_LongTermObligationsCurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsCurrent" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_LongTermObligationsCurrent" xml:lang="en-US" id="ions_LongTermObligationsCurrent">Less: current portion</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsCurrent" xlink:to="ions_LongTermObligationsCurrent" xlink:title="label: LongTermObligationsCurrent to ions_LongTermObligationsCurrent" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LongTermObligationsNoncurrent" xlink:label="LongTermObligationsNoncurrent" xlink:title="LongTermObligationsNoncurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermObligationsNoncurrent_lbl" xml:lang="en-US" id="ions_LongTermObligationsNoncurrent_lbl">Amount of long-term debt, lease obligations and other obligations, classified as noncurrent.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsNoncurrent" xlink:to="ions_LongTermObligationsNoncurrent_lbl" xlink:title="label: LongTermObligationsNoncurrent to ions_LongTermObligationsNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligationsNoncurrent_lbl1" xml:lang="en-US" id="ions_LongTermObligationsNoncurrent_lbl1">Long-term Obligations, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsNoncurrent" xlink:to="ions_LongTermObligationsNoncurrent_lbl1" xlink:title="label: LongTermObligationsNoncurrent to ions_LongTermObligationsNoncurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsNoncurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LongTermObligationsNoncurrent" xml:lang="en-US" id="ions_LongTermObligationsNoncurrent">Total Long-Term Obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsNoncurrent" xlink:to="ions_LongTermObligationsNoncurrent" xlink:title="label: LongTermObligationsNoncurrent to ions_LongTermObligationsNoncurrent" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:label="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:title="LiabilityRelatedToSaleOfFutureRoyaltiesNet" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl">Amount, after accumulated amortization, of the unamortized liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate method.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNet to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl1" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl1">Liability Related to Sale of Future Royalties, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl1" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNet to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet">Liability related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNet to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl2" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl2" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl2">Net liability related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl2" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNet to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl3" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl3">Liability related to sale of future royalties, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl3" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNet to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LongTermObligations" xlink:label="LongTermObligations" xlink:title="LongTermObligations" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligations_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermObligations_lbl" xml:lang="en-US" id="ions_LongTermObligations_lbl">Including the current and noncurrent portions, amount of long-term debt, lease obligations and other obligations.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligations" xlink:to="ions_LongTermObligations_lbl" xlink:title="label: LongTermObligations to ions_LongTermObligations_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligations_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligations_lbl1" xml:lang="en-US" id="ions_LongTermObligations_lbl1">Long-term Obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligations" xlink:to="ions_LongTermObligations_lbl1" xlink:title="label: LongTermObligations to ions_LongTermObligations_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligations" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="ions_LongTermObligations" xml:lang="en-US" id="ions_LongTermObligations">Total</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligations" xlink:to="ions_LongTermObligations" xlink:title="label: LongTermObligations to ions_LongTermObligations" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl">0.125 percent convertible senior notes due December 2024.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl1">Convertible Senior Notes 0.125 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember">0.125% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl2">0.125 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl">0 percent convertible senior notes due April 2026.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl1">Convertible Senior Notes 0 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0PercentMember" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember">0 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl2">0% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_SupplementalFinancialDataAbstract" xlink:label="SupplementalFinancialDataAbstract" xlink:title="SupplementalFinancialDataAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_SupplementalFinancialDataAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SupplementalFinancialDataAbstract_lbl1" xml:lang="en-US" id="ions_SupplementalFinancialDataAbstract_lbl1">Supplemental Financial Data [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SupplementalFinancialDataAbstract" xlink:to="ions_SupplementalFinancialDataAbstract_lbl1" xlink:title="label: SupplementalFinancialDataAbstract to ions_SupplementalFinancialDataAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LessorOperatingLeasePeriodOfFreeRent" xlink:label="LessorOperatingLeasePeriodOfFreeRent" xlink:title="LessorOperatingLeasePeriodOfFreeRent" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeasePeriodOfFreeRent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LessorOperatingLeasePeriodOfFreeRent_lbl" xml:lang="en-US" id="ions_LessorOperatingLeasePeriodOfFreeRent_lbl">Period of time in which the lessor provides free rent under operating lease to the lessee, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeasePeriodOfFreeRent" xlink:to="ions_LessorOperatingLeasePeriodOfFreeRent_lbl" xlink:title="label: LessorOperatingLeasePeriodOfFreeRent to ions_LessorOperatingLeasePeriodOfFreeRent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeasePeriodOfFreeRent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LessorOperatingLeasePeriodOfFreeRent_lbl1" xml:lang="en-US" id="ions_LessorOperatingLeasePeriodOfFreeRent_lbl1">Lessor, Operating Lease, Period of Free Rent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeasePeriodOfFreeRent" xlink:to="ions_LessorOperatingLeasePeriodOfFreeRent_lbl1" xlink:title="label: LessorOperatingLeasePeriodOfFreeRent to ions_LessorOperatingLeasePeriodOfFreeRent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeasePeriodOfFreeRent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LessorOperatingLeasePeriodOfFreeRent" xml:lang="en-US" id="ions_LessorOperatingLeasePeriodOfFreeRent">Period of free rent under sublease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeasePeriodOfFreeRent" xlink:to="ions_LessorOperatingLeasePeriodOfFreeRent" xlink:title="label: LessorOperatingLeasePeriodOfFreeRent to ions_LessorOperatingLeasePeriodOfFreeRent" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AnotherOfficeSpaceInBostonMember" xlink:label="AnotherOfficeSpaceInBostonMember" xlink:title="AnotherOfficeSpaceInBostonMember" />
    <link:label xlink:type="resource" xlink:label="ions_AnotherOfficeSpaceInBostonMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AnotherOfficeSpaceInBostonMember_lbl" xml:lang="en-US" id="ions_AnotherOfficeSpaceInBostonMember_lbl">Another office space located in Boston, Massachusetts leased under non-cancelable operating lease entered into in September 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AnotherOfficeSpaceInBostonMember" xlink:to="ions_AnotherOfficeSpaceInBostonMember_lbl" xlink:title="label: AnotherOfficeSpaceInBostonMember to ions_AnotherOfficeSpaceInBostonMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AnotherOfficeSpaceInBostonMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AnotherOfficeSpaceInBostonMember_lbl1" xml:lang="en-US" id="ions_AnotherOfficeSpaceInBostonMember_lbl1">Another Office Space in Boston [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AnotherOfficeSpaceInBostonMember" xlink:to="ions_AnotherOfficeSpaceInBostonMember_lbl1" xlink:title="label: AnotherOfficeSpaceInBostonMember to ions_AnotherOfficeSpaceInBostonMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_SubleasedOfficeSpaceInBostonMember" xlink:label="SubleasedOfficeSpaceInBostonMember" xlink:title="SubleasedOfficeSpaceInBostonMember" />
    <link:label xlink:type="resource" xlink:label="ions_SubleasedOfficeSpaceInBostonMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SubleasedOfficeSpaceInBostonMember_lbl" xml:lang="en-US" id="ions_SubleasedOfficeSpaceInBostonMember_lbl">Sublease of office space located in Boston, Massachusetts leased under non-cancelable sublease operating lease entered into in January 2022.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubleasedOfficeSpaceInBostonMember" xlink:to="ions_SubleasedOfficeSpaceInBostonMember_lbl" xlink:title="label: SubleasedOfficeSpaceInBostonMember to ions_SubleasedOfficeSpaceInBostonMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SubleasedOfficeSpaceInBostonMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SubleasedOfficeSpaceInBostonMember_lbl1" xml:lang="en-US" id="ions_SubleasedOfficeSpaceInBostonMember_lbl1">Subleased Office Space in Boston [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubleasedOfficeSpaceInBostonMember" xlink:to="ions_SubleasedOfficeSpaceInBostonMember_lbl1" xlink:title="label: SubleasedOfficeSpaceInBostonMember to ions_SubleasedOfficeSpaceInBostonMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:label="NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:title="NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl" xml:lang="en-US" id="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl">Number of lots of undeveloped land adjacent to the Company's headquarters transferred to real estate investor.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:to="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl" xlink:title="label: NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor to ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl1" xml:lang="en-US" id="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl1">Number of lots of undeveloped land transferred to real estate investor</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:to="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl1" xlink:title="label: NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor to ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xml:lang="en-US" id="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor">Number of lots of undeveloped land transferred to real estate investor</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:to="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:title="label: NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor to ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CarlsbadOfficeSpaceMember" xlink:label="CarlsbadOfficeSpaceMember" xlink:title="CarlsbadOfficeSpaceMember" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpaceMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CarlsbadOfficeSpaceMember_lbl" xml:lang="en-US" id="ions_CarlsbadOfficeSpaceMember_lbl">Additional office space in Carlsbad, California leased under non-cancelable operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadOfficeSpaceMember" xlink:to="ions_CarlsbadOfficeSpaceMember_lbl" xlink:title="label: CarlsbadOfficeSpaceMember to ions_CarlsbadOfficeSpaceMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpaceMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CarlsbadOfficeSpaceMember_lbl1" xml:lang="en-US" id="ions_CarlsbadOfficeSpaceMember_lbl1">Carlsbad Office Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadOfficeSpaceMember" xlink:to="ions_CarlsbadOfficeSpaceMember_lbl1" xlink:title="label: CarlsbadOfficeSpaceMember to ions_CarlsbadOfficeSpaceMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpaceMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CarlsbadOfficeSpaceMember" xml:lang="en-US" id="ions_CarlsbadOfficeSpaceMember">Carlsbad Office Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadOfficeSpaceMember" xlink:to="ions_CarlsbadOfficeSpaceMember" xlink:title="label: CarlsbadOfficeSpaceMember to ions_CarlsbadOfficeSpaceMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LesseeOperatingLeasePeriodOfFreeRent" xlink:label="LesseeOperatingLeasePeriodOfFreeRent" xlink:title="LesseeOperatingLeasePeriodOfFreeRent" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl">Period of time in which the rent is free under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1">Lessee, Operating Lease, Period of Free Rent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent">Period of free rent under lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CarlsbadWarehouseSpaceMember" xlink:label="CarlsbadWarehouseSpaceMember" xlink:title="CarlsbadWarehouseSpaceMember" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadWarehouseSpaceMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CarlsbadWarehouseSpaceMember_lbl" xml:lang="en-US" id="ions_CarlsbadWarehouseSpaceMember_lbl">Warehouse space in Carlsbad, California leased under non-cancelable operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadWarehouseSpaceMember" xlink:to="ions_CarlsbadWarehouseSpaceMember_lbl" xlink:title="label: CarlsbadWarehouseSpaceMember to ions_CarlsbadWarehouseSpaceMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadWarehouseSpaceMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CarlsbadWarehouseSpaceMember_lbl1" xml:lang="en-US" id="ions_CarlsbadWarehouseSpaceMember_lbl1">Carlsbad Warehouse Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadWarehouseSpaceMember" xlink:to="ions_CarlsbadWarehouseSpaceMember_lbl1" xlink:title="label: CarlsbadWarehouseSpaceMember to ions_CarlsbadWarehouseSpaceMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadWarehouseSpaceMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CarlsbadWarehouseSpaceMember" xml:lang="en-US" id="ions_CarlsbadWarehouseSpaceMember">Carlsbad Warehouse Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadWarehouseSpaceMember" xlink:to="ions_CarlsbadWarehouseSpaceMember" xlink:title="label: CarlsbadWarehouseSpaceMember to ions_CarlsbadWarehouseSpaceMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:label="LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:title="LessorOperatingLeaseNumberOfOptionsToExtendLease" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl" xml:lang="en-US" id="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl">The number of options to extend the lease under the lessor's operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl" xlink:title="label: LessorOperatingLeaseNumberOfOptionsToExtendLease to ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xml:lang="en-US" id="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl1">Lessor, Operating Lease, Number of options to extend lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xlink:title="label: LessorOperatingLeaseNumberOfOptionsToExtendLease to ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease" xml:lang="en-US" id="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease">Number of options to extend sublease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:title="label: LessorOperatingLeaseNumberOfOptionsToExtendLease to ions_LessorOperatingLeaseNumberOfOptionsToExtendLease" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_HeadquartersLocationInCarlsbadCaliforniaMember" xlink:label="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:title="HeadquartersLocationInCarlsbadCaliforniaMember" />
    <link:label xlink:type="resource" xlink:label="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" xml:lang="en-US" id="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl">Headquarters location located in Carlsbad, California.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:to="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" xlink:title="label: HeadquartersLocationInCarlsbadCaliforniaMember to ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" xml:lang="en-US" id="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1">Headquarters Location in Carlsbad, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:to="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" xlink:title="label: HeadquartersLocationInCarlsbadCaliforniaMember to ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_HeadquartersLocationInCarlsbadCaliforniaMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_HeadquartersLocationInCarlsbadCaliforniaMember" xml:lang="en-US" id="ions_HeadquartersLocationInCarlsbadCaliforniaMember">Headquarters Location in Carlsbad, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:to="ions_HeadquartersLocationInCarlsbadCaliforniaMember" xlink:title="label: HeadquartersLocationInCarlsbadCaliforniaMember to ions_HeadquartersLocationInCarlsbadCaliforniaMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_BostonOfficeSpaceMember" xlink:label="BostonOfficeSpaceMember" xlink:title="BostonOfficeSpaceMember" />
    <link:label xlink:type="resource" xlink:label="ions_BostonOfficeSpaceMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BostonOfficeSpaceMember_lbl" xml:lang="en-US" id="ions_BostonOfficeSpaceMember_lbl">Office space located in Boston, Massachusetts leased under non-cancelable operating lease entered into in the second quarter of 2018..</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BostonOfficeSpaceMember" xlink:to="ions_BostonOfficeSpaceMember_lbl" xlink:title="label: BostonOfficeSpaceMember to ions_BostonOfficeSpaceMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BostonOfficeSpaceMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BostonOfficeSpaceMember_lbl1" xml:lang="en-US" id="ions_BostonOfficeSpaceMember_lbl1">Boston Office Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BostonOfficeSpaceMember" xlink:to="ions_BostonOfficeSpaceMember_lbl1" xlink:title="label: BostonOfficeSpaceMember to ions_BostonOfficeSpaceMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BostonOfficeSpaceMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BostonOfficeSpaceMember" xml:lang="en-US" id="ions_BostonOfficeSpaceMember">Boston Office Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BostonOfficeSpaceMember" xlink:to="ions_BostonOfficeSpaceMember" xlink:title="label: BostonOfficeSpaceMember to ions_BostonOfficeSpaceMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CarlsbadFacilityMember" xlink:label="CarlsbadFacilityMember" xlink:title="CarlsbadFacilityMember" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadFacilityMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CarlsbadFacilityMember_lbl" xml:lang="en-US" id="ions_CarlsbadFacilityMember_lbl">Office and laboratory space in a facility adjacent to the Company's manufacturing facility located in Carlsbad, California leased under non-cancelable operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadFacilityMember" xlink:to="ions_CarlsbadFacilityMember_lbl" xlink:title="label: CarlsbadFacilityMember to ions_CarlsbadFacilityMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadFacilityMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CarlsbadFacilityMember_lbl1" xml:lang="en-US" id="ions_CarlsbadFacilityMember_lbl1">Carlsbad Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadFacilityMember" xlink:to="ions_CarlsbadFacilityMember_lbl1" xlink:title="label: CarlsbadFacilityMember to ions_CarlsbadFacilityMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadFacilityMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CarlsbadFacilityMember" xml:lang="en-US" id="ions_CarlsbadFacilityMember">Carlsbad Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadFacilityMember" xlink:to="ions_CarlsbadFacilityMember" xlink:title="label: CarlsbadFacilityMember to ions_CarlsbadFacilityMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:label="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:title="LesseeOperatingLeaseNumberOfOptionsToExtendLease" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl">The number of options to extend the lease under the lessee's operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" xlink:title="label: LesseeOperatingLeaseNumberOfOptionsToExtendLease to ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1">Lessee, Operating Lease, Number of options to extend lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xlink:title="label: LesseeOperatingLeaseNumberOfOptionsToExtendLease to ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease">Number of options to extend lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:title="label: LesseeOperatingLeaseNumberOfOptionsToExtendLease to ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:label="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:title="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" />
    <link:label xlink:type="resource" xlink:label="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" xml:lang="en-US" id="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl">Development chemistry and manufacturing facility located in Oceanside, California.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:to="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" xlink:title="label: DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember to ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" xml:lang="en-US" id="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1">Development Chemistry and Manufacturing Facility in Oceanside, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:to="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" xlink:title="label: DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember to ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xml:lang="en-US" id="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember">Development Chemistry and Manufacturing Facility in Oceanside, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:to="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:title="label: DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember to ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:label="ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:title="ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl">0.125 percent convertible senior notes due December 2024 that were issued under subscription agreements in December 2019.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember to ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl1">Convertible Senior Notes 0.125 Percent, Issued under Subscription Agreements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember to ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember">0.125% Notes Issued under Subscription Agreements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember to ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember" xlink:label="ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember" xlink:title="ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl">Portion of total proceeds from the issuance of 0 percent convertible senior notes due April 2026 used to pay the remaining principal balance of the 1 percent convertible senior notes due November 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember" xlink:to="ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl" xlink:title="label: ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember to ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl" />
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember" xlink:label="ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember" xlink:title="ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember_lbl">Portion of total proceeds from the issuance of 1.75 percent convertible senior notes due June 2028 used to repurchase a portion of the 0.125 percent convertible senior notes due December 2024.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember_lbl1">Convertible Senior Notes 1.75 Percent, Used to Repurchase 0.125 Percent Convertible Senior Notes [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember">1.75% Notes [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:label="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:title="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl">0.125 percent convertible senior notes due December 2024 that were issued in exchange for 1 percent notes in December 2019.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1">Convertible Senior Notes 0.125 Percent, Issued in Exchange for 1 Percent Notes [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ConvertibleSeniorNotesMember" xlink:label="ConvertibleSeniorNotesMember" xlink:title="ConvertibleSeniorNotesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotesMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotesMember_lbl">Includes 0% convertible senior notes due April 2026, 0.125% convertible senior notes due December 2024, and 1% convertible senior notes due November 2021.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotesMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotesMember_lbl1">Convertible Senior Notes [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotesMember" xml:lang="en-US" id="ions_ConvertibleSeniorNotesMember">Convertible Senior Notes [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DebtInstrumentConvertibleSharesSubjectToConversion" xlink:label="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:title="DebtInstrumentConvertibleSharesSubjectToConversion" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:to="ions_DebtInstrumentConvertibleSharesSubjectToConversion" xlink:title="label: DebtInstrumentConvertibleSharesSubjectToConversion to ions_DebtInstrumentConvertibleSharesSubjectToConversion" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:label="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:title="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl">The computed conversion price per share of the debt instrument based on the the conversion feature embedded in the debt instrument and the impact of the purchased hedges in the call spread transaction.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread">Effective conversion price per share with call spread (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CallSpread" xlink:label="CallSpread" xlink:title="CallSpread" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CallSpread_lbl" xml:lang="en-US" id="ions_CallSpread_lbl">The net cash outflow from payments for hedge transactions and proceeds from the issuance of warrants. The call spread transaction was entered into to minimize the impact of potential economic dilution upon conversion of the 0.125% notes issued.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:label="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:title="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl">The percentage of the principal amount of the notes to be purchased, plus accrued and unpaid interest, upon the occurrence of certain fundamental changes, as set forth in the indenture governing the convertible notes.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange">Percentage of principal amount used as purchase price upon occurrence of fundamental change</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ConvertibleSeniorNotes1PercentMember" xlink:label="ConvertibleSeniorNotes1PercentMember" xlink:title="ConvertibleSeniorNotes1PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl">1 percent convertible senior notes due November 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl" />
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    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember">1% Notes [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_WainusRoyaltiesMember" xlink:label="WainusRoyaltiesMember" xlink:title="WainusRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_WainusRoyaltiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_WainusRoyaltiesMember_lbl" xml:lang="en-US" id="ions_WainusRoyaltiesMember_lbl">Royalty revenues from the sale of WAINUA (eplontersen).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainusRoyaltiesMember" xlink:to="ions_WainusRoyaltiesMember_lbl" xlink:title="label: WainusRoyaltiesMember to ions_WainusRoyaltiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_WainusRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_WainusRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_WainusRoyaltiesMember_lbl1">WAINUA Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainusRoyaltiesMember" xlink:to="ions_WainusRoyaltiesMember_lbl1" xlink:title="label: WainusRoyaltiesMember to ions_WainusRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_WainusRoyaltiesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_WainusRoyaltiesMember" xml:lang="en-US" id="ions_WainusRoyaltiesMember">WAINUA Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainusRoyaltiesMember" xlink:to="ions_WainusRoyaltiesMember" xlink:title="label: WainusRoyaltiesMember to ions_WainusRoyaltiesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:label="InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:title="InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl">Amount of interest expense using the effective interest rate method and amortization of issuance costs related to the sale of future royalties.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xlink:title="label: InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties to ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" xml:lang="en-US" id="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1">Interest Expense and Amortization of Issuance Costs Related to Sale of Future Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" xlink:title="label: InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties to ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xml:lang="en-US" id="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties">Interest expense related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:title="label: InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties to ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ResearchDevelopmentAndPatentExpense" xlink:label="ResearchDevelopmentAndPatentExpense" xlink:title="ResearchDevelopmentAndPatentExpense" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentExpense_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense_lbl">The aggregate costs incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process whether intended for sale or the entity's use, during the reporting period charged to research and development projects. Also includes charges for amortization and write-downs of capitalized patent costs, as well as legal fees for patent litigation and patent defense.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense_lbl" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchDevelopmentAndPatentExpense_lbl1" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense_lbl1">Research, Development and Patent Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense_lbl1" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchDevelopmentAndPatentExpense" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense">Research, development and patent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_WainuaJointDevelopmentRevenueMember" xlink:label="WainuaJointDevelopmentRevenueMember" xlink:title="WainuaJointDevelopmentRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_WainuaJointDevelopmentRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_WainuaJointDevelopmentRevenueMember_lbl" xml:lang="en-US" id="ions_WainuaJointDevelopmentRevenueMember_lbl">Joint development revenue for WAINUA (eplontersen).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainuaJointDevelopmentRevenueMember" xlink:to="ions_WainuaJointDevelopmentRevenueMember_lbl" xlink:title="label: WainuaJointDevelopmentRevenueMember to ions_WainuaJointDevelopmentRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_WainuaJointDevelopmentRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_WainuaJointDevelopmentRevenueMember_lbl1" xml:lang="en-US" id="ions_WainuaJointDevelopmentRevenueMember_lbl1">WAINUA Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainuaJointDevelopmentRevenueMember" xlink:to="ions_WainuaJointDevelopmentRevenueMember_lbl1" xlink:title="label: WainuaJointDevelopmentRevenueMember to ions_WainuaJointDevelopmentRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_WainuaJointDevelopmentRevenueMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_WainuaJointDevelopmentRevenueMember" xml:lang="en-US" id="ions_WainuaJointDevelopmentRevenueMember">WAINUA Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainuaJointDevelopmentRevenueMember" xlink:to="ions_WainuaJointDevelopmentRevenueMember" xlink:title="label: WainuaJointDevelopmentRevenueMember to ions_WainuaJointDevelopmentRevenueMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CommercialMember" xlink:label="CommercialMember" xlink:title="CommercialMember" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CommercialMember_lbl" xml:lang="en-US" id="ions_CommercialMember_lbl">Revenue from the sale of medicines commercially as well as licensing and royalty revenues from other medicines, including SPINRAZA..</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialMember" xlink:to="ions_CommercialMember_lbl" xlink:title="label: CommercialMember to ions_CommercialMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CommercialMember_lbl1" xml:lang="en-US" id="ions_CommercialMember_lbl1">Commercial [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialMember" xlink:to="ions_CommercialMember_lbl1" xlink:title="label: CommercialMember to ions_CommercialMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CommercialMember" xml:lang="en-US" id="ions_CommercialMember">Commercial Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialMember" xlink:to="ions_CommercialMember" xlink:title="label: CommercialMember to ions_CommercialMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_SpinrazaRoyaltiesMember" xlink:label="SpinrazaRoyaltiesMember" xlink:title="SpinrazaRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SpinrazaRoyaltiesMember_lbl" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember_lbl">Royalty revenues from the sale of SPINRAZA (nusinersen).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember_lbl" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SpinrazaRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember_lbl1">SPINRAZA Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember_lbl1" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SpinrazaRoyaltiesMember" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember">SPINRAZA Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ResearchAndDevelopmentRevenueMember" xlink:label="ResearchAndDevelopmentRevenueMember" xlink:title="ResearchAndDevelopmentRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl">Revenue from research and development services.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl1">Research and Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl1" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueMember" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember">Research and Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CollaborativeAgreementRevenueMember" xlink:label="CollaborativeAgreementRevenueMember" xlink:title="CollaborativeAgreementRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeAgreementRevenueMember_lbl" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember_lbl">Revenue from research and development services performed under a collaborative agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember_lbl" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeAgreementRevenueMember_lbl1" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember_lbl1">Collaborative Agreement Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember_lbl1" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeAgreementRevenueMember" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember">Collaborative Agreement Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_OtherCommercialMember" xlink:label="OtherCommercialMember" xlink:title="OtherCommercialMember" />
    <link:label xlink:type="resource" xlink:label="ions_OtherCommercialMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtherCommercialMember_lbl" xml:lang="en-US" id="ions_OtherCommercialMember_lbl">Revenue from the sale of other medicines commercially as well as licensing and royalty revenue from other medicines, including TEGSEDI and WAYLIVRA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCommercialMember" xlink:to="ions_OtherCommercialMember_lbl" xlink:title="label: OtherCommercialMember to ions_OtherCommercialMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtherCommercialMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtherCommercialMember_lbl1" xml:lang="en-US" id="ions_OtherCommercialMember_lbl1">Other Commercial [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCommercialMember" xlink:to="ions_OtherCommercialMember_lbl1" xlink:title="label: OtherCommercialMember to ions_OtherCommercialMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OtherCommercialMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OtherCommercialMember" xml:lang="en-US" id="ions_OtherCommercialMember">Other Commercial Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCommercialMember" xlink:to="ions_OtherCommercialMember" xlink:title="label: OtherCommercialMember to ions_OtherCommercialMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ThreeSignificantCustomersMember" xlink:label="ThreeSignificantCustomersMember" xlink:title="ThreeSignificantCustomersMember" />
    <link:label xlink:type="resource" xlink:label="ions_ThreeSignificantCustomersMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ThreeSignificantCustomersMember_lbl" xml:lang="en-US" id="ions_ThreeSignificantCustomersMember_lbl">Three significant corporate partners and leading global pharmaceutical companies that are working alongside the Company to develop the Company's drugs, advance the Company's technology, and prepare to commercialize and sell the Company's drugs under collaborative arrangement and licensing agreements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ThreeSignificantCustomersMember" xlink:to="ions_ThreeSignificantCustomersMember_lbl" xlink:title="label: ThreeSignificantCustomersMember to ions_ThreeSignificantCustomersMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ThreeSignificantCustomersMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ThreeSignificantCustomersMember_lbl1" xml:lang="en-US" id="ions_ThreeSignificantCustomersMember_lbl1">Three Significant Customers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ThreeSignificantCustomersMember" xlink:to="ions_ThreeSignificantCustomersMember_lbl1" xlink:title="label: ThreeSignificantCustomersMember to ions_ThreeSignificantCustomersMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ThreeSignificantCustomersMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ThreeSignificantCustomersMember" xml:lang="en-US" id="ions_ThreeSignificantCustomersMember">Three Significant Customers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ThreeSignificantCustomersMember" xlink:to="ions_ThreeSignificantCustomersMember" xlink:title="label: ThreeSignificantCustomersMember to ions_ThreeSignificantCustomersMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived" xlink:label="NumberOfQuartersAfterBillingWhenPaymentIsReceived" xlink:title="NumberOfQuartersAfterBillingWhenPaymentIsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived_lbl" xml:lang="en-US" id="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived_lbl">Number of quarters after billing when payment is received from the Company's partner or customer.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfQuartersAfterBillingWhenPaymentIsReceived" xlink:to="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived_lbl" xlink:title="label: NumberOfQuartersAfterBillingWhenPaymentIsReceived to ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived_lbl1" xml:lang="en-US" id="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived_lbl1">Number of quarters after billing when payment is received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfQuartersAfterBillingWhenPaymentIsReceived" xlink:to="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived_lbl1" xlink:title="label: NumberOfQuartersAfterBillingWhenPaymentIsReceived to ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived" xml:lang="en-US" id="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived">Number of quarters after billing when payment is received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfQuartersAfterBillingWhenPaymentIsReceived" xlink:to="ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived" xlink:title="label: NumberOfQuartersAfterBillingWhenPaymentIsReceived to ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfSignificantCustomers" xlink:label="NumberOfSignificantCustomers" xlink:title="NumberOfSignificantCustomers" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfSignificantCustomers_lbl" xml:lang="en-US" id="ions_NumberOfSignificantCustomers_lbl">The number of significant customers with which the Company does business.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers_lbl" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfSignificantCustomers_lbl1" xml:lang="en-US" id="ions_NumberOfSignificantCustomers_lbl1">Number of Significant Customers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers_lbl1" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfSignificantCustomers" xml:lang="en-US" id="ions_NumberOfSignificantCustomers">Number of significant customers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_OneSignificantCustomerMember" xlink:label="OneSignificantCustomerMember" xlink:title="OneSignificantCustomerMember" />
    <link:label xlink:type="resource" xlink:label="ions_OneSignificantCustomerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OneSignificantCustomerMember_lbl" xml:lang="en-US" id="ions_OneSignificantCustomerMember_lbl">One significant corporate partner and leading global pharmaceutical company that is working alongside the Company to develop the Company's medicines, advance the Company's technology, and prepare to commercialize and sell the Company's medicines under collaborative arrangement and licensing agreements.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_OneSignificantCustomerMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OneSignificantCustomerMember" xml:lang="en-US" id="ions_OneSignificantCustomerMember">One Significant Customer [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" xlink:label="DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" xlink:title="DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl" xml:lang="en-US" id="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl">Amount before allocation of valuation allowances of deferred tax asset attributable to capitalized research and development expenses.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DeferredTaxAssetsSaleOfFutureRoyalties" xlink:label="DeferredTaxAssetsSaleOfFutureRoyalties" xlink:title="DeferredTaxAssetsSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeferredTaxAssetsSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_DeferredTaxAssetsSaleOfFutureRoyalties_lbl">Amount before allocation of valuation allowances of deferred tax asset attributable to the sale of future royalties.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsSaleOfFutureRoyalties" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DeferredTaxAssetsSaleOfFutureRoyalties" xml:lang="en-US" id="ions_DeferredTaxAssetsSaleOfFutureRoyalties">Sale of future royalties</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DeferredTaxAssetsFinancingArrangements" xlink:label="DeferredTaxAssetsFinancingArrangements" xlink:title="DeferredTaxAssetsFinancingArrangements" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsFinancingArrangements_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeferredTaxAssetsFinancingArrangements_lbl" xml:lang="en-US" id="ions_DeferredTaxAssetsFinancingArrangements_lbl">Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from financing arrangements.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsFinancingArrangements_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DeferredTaxAssetsFinancingArrangements_lbl1" xml:lang="en-US" id="ions_DeferredTaxAssetsFinancingArrangements_lbl1">Deferred Tax Assets, Financing Arrangements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsFinancingArrangements" xlink:to="ions_DeferredTaxAssetsFinancingArrangements_lbl1" xlink:title="label: DeferredTaxAssetsFinancingArrangements to ions_DeferredTaxAssetsFinancingArrangements_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsFinancingArrangements" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DeferredTaxAssetsFinancingArrangements" xml:lang="en-US" id="ions_DeferredTaxAssetsFinancingArrangements">Convertible debt</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:label="DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:title="DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl" xml:lang="en-US" id="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl">Represents the net amount of deferred tax assets (before reduction for valuation allowance) and liabilities as of the balance sheet date, which result from applying the applicable enacted tax rate to net temporary differences and carryforwards pertaining to assets or liabilities.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl1" xml:lang="en-US" id="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl1">Deferred Tax Assets (Liabilities), Net, before Valuation Allowance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:to="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl1" xlink:title="label: DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance to ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xml:lang="en-US" id="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance">Net deferred tax asset</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:to="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:title="label: DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance to ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DeferredTaxAssetsLeasingArrangements" xlink:label="DeferredTaxAssetsLeasingArrangements" xlink:title="DeferredTaxAssetsLeasingArrangements" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsLeasingArrangements_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeferredTaxAssetsLeasingArrangements_lbl" xml:lang="en-US" id="ions_DeferredTaxAssetsLeasingArrangements_lbl">Amount before allocation of valuation allowances of deferred tax asset attributable to leasing arrangements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsLeasingArrangements" xlink:to="ions_DeferredTaxAssetsLeasingArrangements_lbl" xlink:title="label: DeferredTaxAssetsLeasingArrangements to ions_DeferredTaxAssetsLeasingArrangements_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsLeasingArrangements_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DeferredTaxAssetsLeasingArrangements_lbl1" xml:lang="en-US" id="ions_DeferredTaxAssetsLeasingArrangements_lbl1">Deferred Tax Assets, Leasing Arrangements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsLeasingArrangements" xlink:to="ions_DeferredTaxAssetsLeasingArrangements_lbl1" xlink:title="label: DeferredTaxAssetsLeasingArrangements to ions_DeferredTaxAssetsLeasingArrangements_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsLeasingArrangements" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DeferredTaxAssetsLeasingArrangements" xml:lang="en-US" id="ions_DeferredTaxAssetsLeasingArrangements">Long-term lease liabilities</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent" xlink:label="EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent" xlink:title="EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent" />
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    <link:label xlink:type="resource" xlink:label="ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent_lbl1" xml:lang="en-US" id="ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent_lbl1">Effective Income Tax Rate Reconciliation, Nondeductible Expense, Excess Compensation, Percent</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount" xlink:label="EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount" xlink:title="EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount" />
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RoyaltyRevenueMonetizationAbstract" xlink:label="RoyaltyRevenueMonetizationAbstract" xlink:title="RoyaltyRevenueMonetizationAbstract" />
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    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1">Maximum amount of annual sales on which royalty payments are paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:to="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" xlink:title="label: MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid to ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xml:lang="en-US" id="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid">Maximum amount of annual sales on which royalty payments are paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:to="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:title="label: MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid to ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_SpinrazaMember" xlink:label="SpinrazaMember" xlink:title="SpinrazaMember" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SpinrazaMember_lbl" xml:lang="en-US" id="ions_SpinrazaMember_lbl">Nusinersen, marketed as Spinraza, is a medicine used in treating spinal muscular atrophy (SMA), a progressive, debilitating and often fatal genetic disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaMember" xlink:to="ions_SpinrazaMember_lbl" xlink:title="label: SpinrazaMember to ions_SpinrazaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SpinrazaMember_lbl1" xml:lang="en-US" id="ions_SpinrazaMember_lbl1">SPINRAZA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaMember" xlink:to="ions_SpinrazaMember_lbl1" xlink:title="label: SpinrazaMember to ions_SpinrazaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SpinrazaMember" xml:lang="en-US" id="ions_SpinrazaMember">SPINRAZA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaMember" xlink:to="ions_SpinrazaMember" xlink:title="label: SpinrazaMember to ions_SpinrazaMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:label="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:title="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl">The percentage of royalty payments paid on annual sales of medicine.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:to="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1">Percentage of royalty payments paid on annual sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:to="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine">Percentage of royalty payments paid to Royalty Pharma on annual sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:to="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl2" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl2">Percentage of royalty payments paid on annual sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:to="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl2" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl">The maximum amount of payments receivable for additional milestones under the royalty purchase agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForAdditionalMilestones to ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1">Maximum amount of payments receivable for additional milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForAdditionalMilestones to ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:label="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:title="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" xml:lang="en-US" id="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl">Maximum royalty payments under the royalty purchase agreement made before royalty interest reverts back to the Company.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:to="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" xlink:title="label: MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack to ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" xml:lang="en-US" id="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1">Maximum royalty payments made before royalty interest reverts back</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:to="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" xlink:title="label: MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack to ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xml:lang="en-US" id="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack">Maximum royalty payments made before royalty interest reverts back</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:to="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:title="label: MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack to ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_UpfrontRoyaltyPaymentReceived" xlink:label="UpfrontRoyaltyPaymentReceived" xlink:title="UpfrontRoyaltyPaymentReceived" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontRoyaltyPaymentReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontRoyaltyPaymentReceived_lbl" xml:lang="en-US" id="ions_UpfrontRoyaltyPaymentReceived_lbl">The amount of upfront payments received during the period under the royalty purchase agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontRoyaltyPaymentReceived" xlink:to="ions_UpfrontRoyaltyPaymentReceived_lbl" xlink:title="label: UpfrontRoyaltyPaymentReceived to ions_UpfrontRoyaltyPaymentReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontRoyaltyPaymentReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontRoyaltyPaymentReceived_lbl1" xml:lang="en-US" id="ions_UpfrontRoyaltyPaymentReceived_lbl1">Upfront royalty payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontRoyaltyPaymentReceived" xlink:to="ions_UpfrontRoyaltyPaymentReceived_lbl1" xlink:title="label: UpfrontRoyaltyPaymentReceived to ions_UpfrontRoyaltyPaymentReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontRoyaltyPaymentReceived" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontRoyaltyPaymentReceived" xml:lang="en-US" id="ions_UpfrontRoyaltyPaymentReceived">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontRoyaltyPaymentReceived" xlink:to="ions_UpfrontRoyaltyPaymentReceived" xlink:title="label: UpfrontRoyaltyPaymentReceived to ions_UpfrontRoyaltyPaymentReceived" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PelacarsenMember" xlink:label="PelacarsenMember" xlink:title="PelacarsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PelacarsenMember_lbl" xml:lang="en-US" id="ions_PelacarsenMember_lbl">Pelacarsen, also known as IONIS-APO(a)-L, AKCEA-APO(a)-L, and TQJ230, is an investigational antisense medicine designed to reduce apolipoprotein(a) in the liver in patients suffering from high levels of the lipoprotein Lp(a).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenMember" xlink:to="ions_PelacarsenMember_lbl" xlink:title="label: PelacarsenMember to ions_PelacarsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PelacarsenMember_lbl1" xml:lang="en-US" id="ions_PelacarsenMember_lbl1">Pelacarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenMember" xlink:to="ions_PelacarsenMember_lbl1" xlink:title="label: PelacarsenMember to ions_PelacarsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PelacarsenMember" xml:lang="en-US" id="ions_PelacarsenMember">Pelacarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenMember" xlink:to="ions_PelacarsenMember" xlink:title="label: PelacarsenMember to ions_PelacarsenMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RoyaltyPurchaseAgreementMember" xlink:label="RoyaltyPurchaseAgreementMember" xlink:title="RoyaltyPurchaseAgreementMember" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPurchaseAgreementMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPurchaseAgreementMember_lbl" xml:lang="en-US" id="ions_RoyaltyPurchaseAgreementMember_lbl">In January 2023, the Company entered into a royalty purchase agreement with Royalty Pharma to monetize a portion of future SPINRAZA and pelacarsen royalties the Company is entitled to under arrangements with Biogen and Novartis, respectively.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPurchaseAgreementMember" xlink:to="ions_RoyaltyPurchaseAgreementMember_lbl" xlink:title="label: RoyaltyPurchaseAgreementMember to ions_RoyaltyPurchaseAgreementMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPurchaseAgreementMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPurchaseAgreementMember_lbl1" xml:lang="en-US" id="ions_RoyaltyPurchaseAgreementMember_lbl1">Royalty Purchase Agreement [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPurchaseAgreementMember" xlink:to="ions_RoyaltyPurchaseAgreementMember_lbl1" xlink:title="label: RoyaltyPurchaseAgreementMember to ions_RoyaltyPurchaseAgreementMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPurchaseAgreementMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPurchaseAgreementMember" xml:lang="en-US" id="ions_RoyaltyPurchaseAgreementMember">Royalty Purchase Agreement [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPurchaseAgreementMember" xlink:to="ions_RoyaltyPurchaseAgreementMember" xlink:title="label: RoyaltyPurchaseAgreementMember to ions_RoyaltyPurchaseAgreementMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:label="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:title="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl">The cash outflow paid to third parties for transaction costs in connection with a monetization transaction of future SPINRAZA and pelacarsen royalties the Company is entitled to under collaboration and licensing agreements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl" xlink:title="label: PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties to ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl1" xml:lang="en-US" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl1">Payments for Transaction Costs Related to Sale of Future Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl1" xlink:title="label: PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties to ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xml:lang="en-US" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties">Payments of transaction costs related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:title="label: PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties to ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl2" xml:lang="en-US" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl2">Transaction costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl2" xlink:title="label: PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties to ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl3" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl3" xml:lang="en-US" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl3">Issuance costs related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl3" xlink:title="label: PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties to ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:label="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:title="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl">Amount of amortization expense attributable to the sale of future royalties.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xlink:title="label: AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties to ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" xml:lang="en-US" id="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1">Amortization of Issuance Costs Related to Sale of Future Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" xlink:title="label: AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties to ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xml:lang="en-US" id="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties">Amortization of issuance costs related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:title="label: AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties to ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ProceedsFromSaleOfFutureRoyalties" xlink:label="ProceedsFromSaleOfFutureRoyalties" xlink:title="ProceedsFromSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ProceedsFromSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_ProceedsFromSaleOfFutureRoyalties_lbl">The cash inflow from the sale of future royalties under a royalty purchase agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfFutureRoyalties" xlink:to="ions_ProceedsFromSaleOfFutureRoyalties_lbl" xlink:title="label: ProceedsFromSaleOfFutureRoyalties to ions_ProceedsFromSaleOfFutureRoyalties_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfFutureRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ProceedsFromSaleOfFutureRoyalties_lbl1" xml:lang="en-US" id="ions_ProceedsFromSaleOfFutureRoyalties_lbl1">Proceeds from Sale of Future Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfFutureRoyalties" xlink:to="ions_ProceedsFromSaleOfFutureRoyalties_lbl1" xlink:title="label: ProceedsFromSaleOfFutureRoyalties to ions_ProceedsFromSaleOfFutureRoyalties_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfFutureRoyalties" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ProceedsFromSaleOfFutureRoyalties" xml:lang="en-US" id="ions_ProceedsFromSaleOfFutureRoyalties">Proceeds from sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfFutureRoyalties" xlink:to="ions_ProceedsFromSaleOfFutureRoyalties" xlink:title="label: ProceedsFromSaleOfFutureRoyalties to ions_ProceedsFromSaleOfFutureRoyalties" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RoyaltyPayments" xlink:label="RoyaltyPayments" xlink:title="RoyaltyPayments" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPayments_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPayments_lbl" xml:lang="en-US" id="ions_RoyaltyPayments_lbl">The amount of royalty payments made during the period under a royalty purchase agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPayments" xlink:to="ions_RoyaltyPayments_lbl" xlink:title="label: RoyaltyPayments to ions_RoyaltyPayments_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPayments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPayments_lbl1" xml:lang="en-US" id="ions_RoyaltyPayments_lbl1">Royalty Payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPayments" xlink:to="ions_RoyaltyPayments_lbl1" xlink:title="label: RoyaltyPayments to ions_RoyaltyPayments_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPayments" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="ions_RoyaltyPayments" xml:lang="en-US" id="ions_RoyaltyPayments">Non-cash royalty revenue related to sale of royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPayments" xlink:to="ions_RoyaltyPayments" xlink:title="label: RoyaltyPayments to ions_RoyaltyPayments" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPayments_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_RoyaltyPayments_lbl2" xml:lang="en-US" id="ions_RoyaltyPayments_lbl2">Royalty payments to Royalty Pharma</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPayments" xlink:to="ions_RoyaltyPayments_lbl2" xlink:title="label: RoyaltyPayments to ions_RoyaltyPayments_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:label="InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:title="InterestExpenseRelatedToSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl">Amount of interest expense using the effective interest rate method related to the sale of future royalties.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:to="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl" xlink:title="label: InterestExpenseRelatedToSaleOfFutureRoyalties to ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl1" xml:lang="en-US" id="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl1">Interest Expense Related to Sale of Future Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:to="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl1" xlink:title="label: InterestExpenseRelatedToSaleOfFutureRoyalties to ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_InterestExpenseRelatedToSaleOfFutureRoyalties" xml:lang="en-US" id="ions_InterestExpenseRelatedToSaleOfFutureRoyalties">Non-cash interest related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:to="ions_InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:title="label: InterestExpenseRelatedToSaleOfFutureRoyalties to ions_InterestExpenseRelatedToSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl2" xml:lang="en-US" id="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl2">Interest expense related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:to="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl2" xlink:title="label: InterestExpenseRelatedToSaleOfFutureRoyalties to ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MeasurementPeriodForAlternativePayoutMechanism" xlink:label="MeasurementPeriodForAlternativePayoutMechanism" xlink:title="MeasurementPeriodForAlternativePayoutMechanism" />
    <link:label xlink:type="resource" xlink:label="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl" xml:lang="en-US" id="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl">Measurement period for alternative payout mechanism, or the Alternative Calculation, included in equity-based award, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MeasurementPeriodForAlternativePayoutMechanism" xlink:to="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl" xlink:title="label: MeasurementPeriodForAlternativePayoutMechanism to ions_MeasurementPeriodForAlternativePayoutMechanism_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl1" xml:lang="en-US" id="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl1">Measurement Period for Alternative Payout Mechanism</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MeasurementPeriodForAlternativePayoutMechanism" xlink:to="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl1" xlink:title="label: MeasurementPeriodForAlternativePayoutMechanism to ions_MeasurementPeriodForAlternativePayoutMechanism_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MeasurementPeriodForAlternativePayoutMechanism" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MeasurementPeriodForAlternativePayoutMechanism" xml:lang="en-US" id="ions_MeasurementPeriodForAlternativePayoutMechanism">Measurement period for Alternative Calculation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MeasurementPeriodForAlternativePayoutMechanism" xlink:to="ions_MeasurementPeriodForAlternativePayoutMechanism" xlink:title="label: MeasurementPeriodForAlternativePayoutMechanism to ions_MeasurementPeriodForAlternativePayoutMechanism" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_TermOfAlternativePayoutMechanism" xlink:label="TermOfAlternativePayoutMechanism" xlink:title="TermOfAlternativePayoutMechanism" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfAlternativePayoutMechanism_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TermOfAlternativePayoutMechanism_lbl" xml:lang="en-US" id="ions_TermOfAlternativePayoutMechanism_lbl">Term of an alternative three-year payout mechanism, or the Alternative Calculation, included in equity-based award, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfAlternativePayoutMechanism" xlink:to="ions_TermOfAlternativePayoutMechanism_lbl" xlink:title="label: TermOfAlternativePayoutMechanism to ions_TermOfAlternativePayoutMechanism_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfAlternativePayoutMechanism_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TermOfAlternativePayoutMechanism_lbl1" xml:lang="en-US" id="ions_TermOfAlternativePayoutMechanism_lbl1">Term of Alternative Payout Mechanism</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfAlternativePayoutMechanism" xlink:to="ions_TermOfAlternativePayoutMechanism_lbl1" xlink:title="label: TermOfAlternativePayoutMechanism to ions_TermOfAlternativePayoutMechanism_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfAlternativePayoutMechanism" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TermOfAlternativePayoutMechanism" xml:lang="en-US" id="ions_TermOfAlternativePayoutMechanism">Term of Alternative Calculation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfAlternativePayoutMechanism" xlink:to="ions_TermOfAlternativePayoutMechanism" xlink:title="label: TermOfAlternativePayoutMechanism to ions_TermOfAlternativePayoutMechanism" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_GrantedAtInitialAppointmentMember" xlink:label="GrantedAtInitialAppointmentMember" xlink:title="GrantedAtInitialAppointmentMember" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedAtInitialAppointmentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GrantedAtInitialAppointmentMember_lbl" xml:lang="en-US" id="ions_GrantedAtInitialAppointmentMember_lbl">Awards granted at initial appointment to the board of directors.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedAtInitialAppointmentMember" xlink:to="ions_GrantedAtInitialAppointmentMember_lbl" xlink:title="label: GrantedAtInitialAppointmentMember to ions_GrantedAtInitialAppointmentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedAtInitialAppointmentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GrantedAtInitialAppointmentMember_lbl1" xml:lang="en-US" id="ions_GrantedAtInitialAppointmentMember_lbl1">Granted at Initial Appointment [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedAtInitialAppointmentMember" xlink:to="ions_GrantedAtInitialAppointmentMember_lbl1" xlink:title="label: GrantedAtInitialAppointmentMember to ions_GrantedAtInitialAppointmentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedAtInitialAppointmentMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GrantedAtInitialAppointmentMember" xml:lang="en-US" id="ions_GrantedAtInitialAppointmentMember">Granted at Initial Appointment [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedAtInitialAppointmentMember" xlink:to="ions_GrantedAtInitialAppointmentMember" xlink:title="label: GrantedAtInitialAppointmentMember to ions_GrantedAtInitialAppointmentMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_Granted2020Through2022Member" xlink:label="Granted2020Through2022Member" xlink:title="Granted2020Through2022Member" />
    <link:label xlink:type="resource" xlink:label="ions_Granted2020Through2022Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Granted2020Through2022Member_lbl" xml:lang="en-US" id="ions_Granted2020Through2022Member_lbl">Awards granted in 2020 through 2022.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Granted2020Through2022Member" xlink:to="ions_Granted2020Through2022Member_lbl" xlink:title="label: Granted2020Through2022Member to ions_Granted2020Through2022Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Granted2020Through2022Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Granted2020Through2022Member_lbl1" xml:lang="en-US" id="ions_Granted2020Through2022Member_lbl1">Granted 2020 through 2022 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Granted2020Through2022Member" xlink:to="ions_Granted2020Through2022Member_lbl1" xlink:title="label: Granted2020Through2022Member to ions_Granted2020Through2022Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Granted2020Through2022Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Granted2020Through2022Member" xml:lang="en-US" id="ions_Granted2020Through2022Member">Granted 2020 through 2022 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Granted2020Through2022Member" xlink:to="ions_Granted2020Through2022Member" xlink:title="label: Granted2020Through2022Member to ions_Granted2020Through2022Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_GrantedIn2024And2023Member" xlink:label="GrantedIn2024And2023Member" xlink:title="GrantedIn2024And2023Member" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2024And2023Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GrantedIn2024And2023Member_lbl" xml:lang="en-US" id="ions_GrantedIn2024And2023Member_lbl">Awards granted in 2024 and 2023.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedIn2024And2023Member" xlink:to="ions_GrantedIn2024And2023Member_lbl" xlink:title="label: GrantedIn2024And2023Member to ions_GrantedIn2024And2023Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2024And2023Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GrantedIn2024And2023Member_lbl1" xml:lang="en-US" id="ions_GrantedIn2024And2023Member_lbl1">Granted in 2024 and 2023 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedIn2024And2023Member" xlink:to="ions_GrantedIn2024And2023Member_lbl1" xlink:title="label: GrantedIn2024And2023Member to ions_GrantedIn2024And2023Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2024And2023Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GrantedIn2024And2023Member" xml:lang="en-US" id="ions_GrantedIn2024And2023Member">Granted in 2024 and 2023 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedIn2024And2023Member" xlink:to="ions_GrantedIn2024And2023Member" xlink:title="label: GrantedIn2024And2023Member to ions_GrantedIn2024And2023Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ShareBasedPaymentArrangementBoardOfDirectorsMember" xlink:label="ShareBasedPaymentArrangementBoardOfDirectorsMember" xlink:title="ShareBasedPaymentArrangementBoardOfDirectorsMember" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember_lbl" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember_lbl">Recipient, of award granted under share-based payment arrangement, over whom grantor exercises or has right to exercise sufficient control to establish employer-employee relationship based on law of pertinent jurisdiction. Includes nonemployee director treated as employee when acting as member of board of directors, if elected by grantor's shareholders or appointed to board position to be filled by shareholder election when existing term expires.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementBoardOfDirectorsMember" xlink:to="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember_lbl" xlink:title="label: ShareBasedPaymentArrangementBoardOfDirectorsMember to ions_ShareBasedPaymentArrangementBoardOfDirectorsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember_lbl1" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember_lbl1">Share-based Payment Arrangement, Board of Directors [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementBoardOfDirectorsMember" xlink:to="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember_lbl1" xlink:title="label: ShareBasedPaymentArrangementBoardOfDirectorsMember to ions_ShareBasedPaymentArrangementBoardOfDirectorsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember">Board of Directors [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementBoardOfDirectorsMember" xlink:to="ions_ShareBasedPaymentArrangementBoardOfDirectorsMember" xlink:title="label: ShareBasedPaymentArrangementBoardOfDirectorsMember to ions_ShareBasedPaymentArrangementBoardOfDirectorsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_GrantedPriorToJune2020Member" xlink:label="GrantedPriorToJune2020Member" xlink:title="GrantedPriorToJune2020Member" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedPriorToJune2020Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GrantedPriorToJune2020Member_lbl" xml:lang="en-US" id="ions_GrantedPriorToJune2020Member_lbl">Awards granted prior to June 2020.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedPriorToJune2020Member" xlink:to="ions_GrantedPriorToJune2020Member_lbl" xlink:title="label: GrantedPriorToJune2020Member to ions_GrantedPriorToJune2020Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedPriorToJune2020Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GrantedPriorToJune2020Member_lbl1" xml:lang="en-US" id="ions_GrantedPriorToJune2020Member_lbl1">Granted Prior to June 2020 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedPriorToJune2020Member" xlink:to="ions_GrantedPriorToJune2020Member_lbl1" xlink:title="label: GrantedPriorToJune2020Member to ions_GrantedPriorToJune2020Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedPriorToJune2020Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GrantedPriorToJune2020Member" xml:lang="en-US" id="ions_GrantedPriorToJune2020Member">Granted Prior to June 2020 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedPriorToJune2020Member" xlink:to="ions_GrantedPriorToJune2020Member" xlink:title="label: GrantedPriorToJune2020Member to ions_GrantedPriorToJune2020Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_GrantedAfterJune2020Member" xlink:label="GrantedAfterJune2020Member" xlink:title="GrantedAfterJune2020Member" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedAfterJune2020Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GrantedAfterJune2020Member_lbl" xml:lang="en-US" id="ions_GrantedAfterJune2020Member_lbl">Awards granted after June 2020.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" />
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl">Number of units guaranteed to vest under share-based payment arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Number of units guaranteed to vest</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest">Number of units guaranteed to vest (in shares)</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl">Percentage of units guaranteed to vest under share-based payment arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Percentage of units guaranteed to vest</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:label="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:title="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl">Share-based payment arrangement granting right, subject to vesting and other restrictions, to purchase or sell certain number of shares at predetermined price for specified period of time granted on January 1, 2022 and thereafter.</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember to ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:label="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:title="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl">Share-based payment arrangement granting right, subject to vesting and other restrictions, to purchase or sell certain number of shares at predetermined price for specified period of time granted prior to January 1, 2022.</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member to ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_EquipmentAndComputerSoftwareMember" xlink:label="EquipmentAndComputerSoftwareMember" xlink:title="EquipmentAndComputerSoftwareMember" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquipmentAndComputerSoftwareMember" xlink:to="ions_EquipmentAndComputerSoftwareMember_lbl1" xlink:title="label: EquipmentAndComputerSoftwareMember to ions_EquipmentAndComputerSoftwareMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquipmentAndComputerSoftwareMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquipmentAndComputerSoftwareMember" xml:lang="en-US" id="ions_EquipmentAndComputerSoftwareMember">Computer Software, Laboratory, Manufacturing and Other Equipment [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquipmentAndComputerSoftwareMember" xlink:to="ions_EquipmentAndComputerSoftwareMember" xlink:title="label: EquipmentAndComputerSoftwareMember to ions_EquipmentAndComputerSoftwareMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:label="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:title="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl" xml:lang="en-US" id="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl">Period of time to make only payments of interest on the mortgage loan, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xml:lang="en-US" id="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan">Period to make interest only payments on mortgage loan</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:to="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:title="label: PeriodToMakeInterestOnlyPaymentsOnMortgageLoan to ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ManufacturingFacilityMortgageMember" xlink:label="ManufacturingFacilityMortgageMember" xlink:title="ManufacturingFacilityMortgageMember" />
    <link:label xlink:type="resource" xlink:label="ions_ManufacturingFacilityMortgageMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ManufacturingFacilityMortgageMember_lbl" xml:lang="en-US" id="ions_ManufacturingFacilityMortgageMember_lbl">Loan agreement with UBS AG entered into on July 18, 2017 to finance the purchase of the Company's research and development facility.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingFacilityMortgageMember" xlink:to="ions_ManufacturingFacilityMortgageMember_lbl" xlink:title="label: ManufacturingFacilityMortgageMember to ions_ManufacturingFacilityMortgageMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ManufacturingFacilityMortgageMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ManufacturingFacilityMortgageMember_lbl1" xml:lang="en-US" id="ions_ManufacturingFacilityMortgageMember_lbl1">Manufacturing Facility Mortgage [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingFacilityMortgageMember" xlink:to="ions_ManufacturingFacilityMortgageMember_lbl1" xlink:title="label: ManufacturingFacilityMortgageMember to ions_ManufacturingFacilityMortgageMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ManufacturingFacilityMortgageMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ManufacturingFacilityMortgageMember" xml:lang="en-US" id="ions_ManufacturingFacilityMortgageMember">Manufacturing Facility Mortgage [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingFacilityMortgageMember" xlink:to="ions_ManufacturingFacilityMortgageMember" xlink:title="label: ManufacturingFacilityMortgageMember to ions_ManufacturingFacilityMortgageMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:label="PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:title="PrimaryResearchAndDevelopmentFacilityMortgageMember" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl">Loan agreement with UBS AG entered into on July 18, 2017 to finance the purchase of the Company's primary research and development (R&amp;D) facility.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMortgageMember to ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl1" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl1">Primary Research and Development Facility Mortgage [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl1" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMortgageMember to ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember">Primary R&amp;D Facility Mortgage [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMortgageMember to ions_PrimaryResearchAndDevelopmentFacilityMortgageMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:label="NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:title="NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl" xml:lang="en-US" id="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl">The number of purchased facilities financed with mortgage debt.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:to="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl" xlink:title="label: NumberOfPurchasedFacilitiesFinancedWithMortgageDebt to ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl1" xml:lang="en-US" id="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl1">Number of purchased facilities financed with mortgage debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:to="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl1" xlink:title="label: NumberOfPurchasedFacilitiesFinancedWithMortgageDebt to ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xml:lang="en-US" id="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt">Number of purchased facilities financed with mortgage debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:to="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:title="label: NumberOfPurchasedFacilitiesFinancedWithMortgageDebt to ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LongTermMortgageDebtMember" xlink:label="LongTermMortgageDebtMember" xlink:title="LongTermMortgageDebtMember" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermMortgageDebtMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermMortgageDebtMember_lbl" xml:lang="en-US" id="ions_LongTermMortgageDebtMember_lbl">Two loan agreements with UBS AG entered into on July 18, 2017 to finance the purchase of the Company's research and development and manufacturing facilities.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermMortgageDebtMember" xlink:to="ions_LongTermMortgageDebtMember_lbl" xlink:title="label: LongTermMortgageDebtMember to ions_LongTermMortgageDebtMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermMortgageDebtMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermMortgageDebtMember_lbl1" xml:lang="en-US" id="ions_LongTermMortgageDebtMember_lbl1">Long-term Mortgage Debt [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermMortgageDebtMember" xlink:to="ions_LongTermMortgageDebtMember_lbl1" xlink:title="label: LongTermMortgageDebtMember to ions_LongTermMortgageDebtMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermMortgageDebtMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LongTermMortgageDebtMember" xml:lang="en-US" id="ions_LongTermMortgageDebtMember">Long-term Mortgage Debt [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermMortgageDebtMember" xlink:to="ions_LongTermMortgageDebtMember" xlink:title="label: LongTermMortgageDebtMember to ions_LongTermMortgageDebtMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PrimaryResearchAndDevelopmentFacilityMember" xlink:label="PrimaryResearchAndDevelopmentFacilityMember" xlink:title="PrimaryResearchAndDevelopmentFacilityMember" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl">Facility constructed for the entity's primary research and development activities under a lease agreement with an affiliate of BioMed Realty, L.P.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMember to ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1">Primary Research and Development Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMember to ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMember" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMember">Primary R&amp;D Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMember" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMember to ions_PrimaryResearchAndDevelopmentFacilityMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:label="NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:title="NewResearchAndDevelopmentFacilityInCarlsbadCAMember" />
    <link:label xlink:type="resource" xlink:label="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl" xml:lang="en-US" id="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl">New research and development (R&amp;D) facility in Carlsbad, California composed of R&amp;D and office space.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:to="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl" xlink:title="label: NewResearchAndDevelopmentFacilityInCarlsbadCAMember to ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl1" xml:lang="en-US" id="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl1">New Research and Development Facility in Carlsbad, CA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:to="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl1" xlink:title="label: NewResearchAndDevelopmentFacilityInCarlsbadCAMember to ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xml:lang="en-US" id="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember">New R&amp;D Facility in Carlsbad, CA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:to="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:title="label: NewResearchAndDevelopmentFacilityInCarlsbadCAMember to ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:label="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:title="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" xml:lang="en-US" id="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl">Number of purchase and sale agreements entered into with a real estate investor.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:to="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" xlink:title="label: NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor to ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" xml:lang="en-US" id="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1">Number of purchase and sale agreements entered into with real estate investor</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:to="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" xlink:title="label: NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor to ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xml:lang="en-US" id="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor">Number of purchase and sale agreements entered into with real estate investor</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:to="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:title="label: NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor to ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_BoardOfDirectorStockOptionMember" xlink:label="BoardOfDirectorStockOptionMember" xlink:title="BoardOfDirectorStockOptionMember" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BoardOfDirectorStockOptionMember_lbl" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember_lbl">An arrangement whereby a member of the Board of Directors is entitled to receive in the future, subject to vesting and other restrictions, a number of shares in the entity at a specified price, as defined in the agreement, as a form of compensation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember_lbl" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BoardOfDirectorStockOptionMember_lbl1" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember_lbl1">Board of Director Stock Option [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember_lbl1" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BoardOfDirectorStockOptionMember" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember">Board of Director Stock Options [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_IssuedAfterDecember312021Member" xlink:label="IssuedAfterDecember312021Member" xlink:title="IssuedAfterDecember312021Member" />
    <link:label xlink:type="resource" xlink:label="ions_IssuedAfterDecember312021Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IssuedAfterDecember312021Member_lbl" xml:lang="en-US" id="ions_IssuedAfterDecember312021Member_lbl">Awards issued after December 31, 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IssuedAfterDecember312021Member" xlink:to="ions_IssuedAfterDecember312021Member_lbl" xlink:title="label: IssuedAfterDecember312021Member to ions_IssuedAfterDecember312021Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IssuedAfterDecember312021Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IssuedAfterDecember312021Member_lbl1" xml:lang="en-US" id="ions_IssuedAfterDecember312021Member_lbl1">Issued after December 31, 2021 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IssuedAfterDecember312021Member" xlink:to="ions_IssuedAfterDecember312021Member_lbl1" xlink:title="label: IssuedAfterDecember312021Member to ions_IssuedAfterDecember312021Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IssuedAfterDecember312021Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IssuedAfterDecember312021Member" xml:lang="en-US" id="ions_IssuedAfterDecember312021Member">Issued after December 31, 2021 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IssuedAfterDecember312021Member" xlink:to="ions_IssuedAfterDecember312021Member" xlink:title="label: IssuedAfterDecember312021Member to ions_IssuedAfterDecember312021Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_EquityIncentivePlan2011Member" xlink:label="EquityIncentivePlan2011Member" xlink:title="EquityIncentivePlan2011Member" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquityIncentivePlan2011Member_lbl" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member_lbl">Represents the stock option plan that provides for the issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to employees, directors, and consultants.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member_lbl" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquityIncentivePlan2011Member_lbl1" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member_lbl1">Equity Incentive Plan 2011 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member_lbl1" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquityIncentivePlan2011Member" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member">2011 Equity Incentive Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_EquityIncentivePlan2020Member" xlink:label="EquityIncentivePlan2020Member" xlink:title="EquityIncentivePlan2020Member" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2020Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquityIncentivePlan2020Member_lbl" xml:lang="en-US" id="ions_EquityIncentivePlan2020Member_lbl">In December 2020, the Company amended and restated the Akcea 2015 Equity Incentive Plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or 2020 Plan. The 2020 Plan provided for the issuance of up to 2.6 million shares of Common Stock to employees, directors and consultants who were employees of Akcea prior to the Akcea Acquisition.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2020Member" xlink:to="ions_EquityIncentivePlan2020Member_lbl" xlink:title="label: EquityIncentivePlan2020Member to ions_EquityIncentivePlan2020Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2020Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquityIncentivePlan2020Member_lbl1" xml:lang="en-US" id="ions_EquityIncentivePlan2020Member_lbl1">Equity Incentive Plan 2020 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2020Member" xlink:to="ions_EquityIncentivePlan2020Member_lbl1" xlink:title="label: EquityIncentivePlan2020Member to ions_EquityIncentivePlan2020Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2020Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquityIncentivePlan2020Member" xml:lang="en-US" id="ions_EquityIncentivePlan2020Member">2020 Equity Incentive Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2020Member" xlink:to="ions_EquityIncentivePlan2020Member" xlink:title="label: EquityIncentivePlan2020Member to ions_EquityIncentivePlan2020Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl">The weighted average grant-date fair value of options exercised during the reporting period as calculated by applying the disclosed option pricing methodology.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized_lbl1" xml:lang="en-US" id="ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized_lbl1">Number of targets to be researched, developed and commercialized</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PaymentToLicenseTechnology" xlink:label="PaymentToLicenseTechnology" xlink:title="PaymentToLicenseTechnology" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentToLicenseTechnology" xlink:to="ions_PaymentToLicenseTechnology_lbl1" xlink:title="label: PaymentToLicenseTechnology to ions_PaymentToLicenseTechnology_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentToLicenseTechnology" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PaymentToLicenseTechnology" xml:lang="en-US" id="ions_PaymentToLicenseTechnology">Payment to license technology</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentToLicenseTechnology" xlink:to="ions_PaymentToLicenseTechnology" xlink:title="label: PaymentToLicenseTechnology to ions_PaymentToLicenseTechnology" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MetagenomiLicenseAgreementMember" xlink:label="MetagenomiLicenseAgreementMember" xlink:title="MetagenomiLicenseAgreementMember" />
    <link:label xlink:type="resource" xlink:label="ions_MetagenomiLicenseAgreementMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MetagenomiLicenseAgreementMember_lbl" xml:lang="en-US" id="ions_MetagenomiLicenseAgreementMember_lbl">License agreement entered into with Metagenomi in November 2022 to research, develop and commercialize investigational medicines for up to eight potential targets using gene editing technologies.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MetagenomiLicenseAgreementMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MetagenomiLicenseAgreementMember_lbl1" xml:lang="en-US" id="ions_MetagenomiLicenseAgreementMember_lbl1">Metagenomi License Agreement [Member]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MetagenomiLicenseAgreementMember" xlink:to="ions_MetagenomiLicenseAgreementMember" xlink:title="label: MetagenomiLicenseAgreementMember to ions_MetagenomiLicenseAgreementMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock" xlink:label="LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock" xlink:title="LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock to ions_LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CapitalizedMaterialsPolicyPolicyTextBlock" xlink:label="CapitalizedMaterialsPolicyPolicyTextBlock" xlink:title="CapitalizedMaterialsPolicyPolicyTextBlock" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesPolicyPolicyTextBlock" xlink:to="ions_AccruedLiabilitiesPolicyPolicyTextBlock_lbl" xlink:title="label: AccruedLiabilitiesPolicyPolicyTextBlock to ions_AccruedLiabilitiesPolicyPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedLiabilitiesPolicyPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedLiabilitiesPolicyPolicyTextBlock_lbl1" xml:lang="en-US" id="ions_AccruedLiabilitiesPolicyPolicyTextBlock_lbl1">Accrued Liabilities, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesPolicyPolicyTextBlock" xlink:to="ions_AccruedLiabilitiesPolicyPolicyTextBlock_lbl1" xlink:title="label: AccruedLiabilitiesPolicyPolicyTextBlock to ions_AccruedLiabilitiesPolicyPolicyTextBlock_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedLiabilitiesPolicyPolicyTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedLiabilitiesPolicyPolicyTextBlock" xml:lang="en-US" id="ions_AccruedLiabilitiesPolicyPolicyTextBlock">Accrued Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesPolicyPolicyTextBlock" xlink:to="ions_AccruedLiabilitiesPolicyPolicyTextBlock" xlink:title="label: AccruedLiabilitiesPolicyPolicyTextBlock to ions_AccruedLiabilitiesPolicyPolicyTextBlock" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ResearchDevelopmentAndPatentMember" xlink:label="ResearchDevelopmentAndPatentMember" xlink:title="ResearchDevelopmentAndPatentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl">Primary financial statement caption encompassing research, development and patent expenses.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl1" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl1">Research, Development and Patent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl1" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchDevelopmentAndPatentMember" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember">Research, Development and Patent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:label="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl">The number of executive officers terminated by the Company during the period that begins three months before and ends twelve months following a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:title="label: NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1">Number of executive officers terminated before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:title="label: NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers">Number of executive officers terminated before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="label: NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:label="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xml:lang="en-US" id="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl">Period of time before a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:title="label: PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xml:lang="en-US" id="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1">Period before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:title="label: PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xml:lang="en-US" id="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers">Period before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="label: PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:label="PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xml:lang="en-US" id="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl">Period of time after a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:title="label: PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xml:lang="en-US" id="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1">Period after change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:title="label: PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xml:lang="en-US" id="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers">Period after change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="label: PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl">Represents the holding period from the date of purchase for stock purchased under the plan.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Holding Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod">Holding period for purchased stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:label="EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:title="EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl">Weighted average sales price of shares purchased through an employee stock purchase plan.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:to="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl" xlink:title="label: EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased to ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl1" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl1">Employee Stock Purchase Plan, Weighted Average Sales Price of Shares Purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:to="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl1" xlink:title="label: EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased to ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased">Weighted average purchase price (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:to="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:title="label: EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased to ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:label="EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:title="EmployeeStockPurchasePlanSharesAvailableForPurchase" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl">The number of shares available for purchase under an employee stock purchase plan.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:to="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl" xlink:title="label: EmployeeStockPurchasePlanSharesAvailableForPurchase to ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl1" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl1">Employee Stock Purchase Plan, Shares Available for Purchase</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:to="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl1" xlink:title="label: EmployeeStockPurchasePlanSharesAvailableForPurchase to ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase">Shares available for purchase under ESPP (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:to="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:title="label: EmployeeStockPurchasePlanSharesAvailableForPurchase to ions_EmployeeStockPurchasePlanSharesAvailableForPurchase" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NonemployeeDirectorsStockOptionPlan2002Member" xlink:label="NonemployeeDirectorsStockOptionPlan2002Member" xlink:title="NonemployeeDirectorsStockOptionPlan2002Member" />
    <link:label xlink:type="resource" xlink:label="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl" xml:lang="en-US" id="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl">Represents the 2002 Non-Employee Directors Stock Option Plan, which provided for the issuance of stock options to the entity's non-employee directors for the purchase of common stock.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonemployeeDirectorsStockOptionPlan2002Member" xlink:to="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl" xlink:title="label: NonemployeeDirectorsStockOptionPlan2002Member to ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl1" xml:lang="en-US" id="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl1">Nonemployee Directors' Stock Option Plan 2002 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonemployeeDirectorsStockOptionPlan2002Member" xlink:to="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl1" xlink:title="label: NonemployeeDirectorsStockOptionPlan2002Member to ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NonemployeeDirectorsStockOptionPlan2002Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NonemployeeDirectorsStockOptionPlan2002Member" xml:lang="en-US" id="ions_NonemployeeDirectorsStockOptionPlan2002Member">2002 Non-Employee Directors' Stock Option Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonemployeeDirectorsStockOptionPlan2002Member" xlink:to="ions_NonemployeeDirectorsStockOptionPlan2002Member" xlink:title="label: NonemployeeDirectorsStockOptionPlan2002Member to ions_NonemployeeDirectorsStockOptionPlan2002Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_StockOptionPlan1989Member" xlink:label="StockOptionPlan1989Member" xlink:title="StockOptionPlan1989Member" />
    <link:label xlink:type="resource" xlink:label="ions_StockOptionPlan1989Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_StockOptionPlan1989Member_lbl" xml:lang="en-US" id="ions_StockOptionPlan1989Member_lbl">Represents the 1989 Stock Option Plan, which provides the issuance of non-qualified and incentive stock options for the purchase of common stock to the entity's employees, directors and consultants.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockOptionPlan1989Member" xlink:to="ions_StockOptionPlan1989Member_lbl" xlink:title="label: StockOptionPlan1989Member to ions_StockOptionPlan1989Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_StockOptionPlan1989Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_StockOptionPlan1989Member_lbl1" xml:lang="en-US" id="ions_StockOptionPlan1989Member_lbl1">Stock Option Plan 1989 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockOptionPlan1989Member" xlink:to="ions_StockOptionPlan1989Member_lbl1" xlink:title="label: StockOptionPlan1989Member to ions_StockOptionPlan1989Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_StockOptionPlan1989Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_StockOptionPlan1989Member" xml:lang="en-US" id="ions_StockOptionPlan1989Member">1989 Stock Option Plan [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_EmployeeStockPurchasePlanMember" xlink:label="EmployeeStockPurchasePlanMember" xlink:title="EmployeeStockPurchasePlanMember" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EmployeeStockPurchasePlanMember_lbl" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanMember_lbl">Represents the 2009 Employee Stock Purchase Plan, as amended and restated, which permits full-time employees to purchase common stock through payroll deductions at a percentage of the fair market value.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanMember" xlink:to="ions_EmployeeStockPurchasePlanMember_lbl" xlink:title="label: EmployeeStockPurchasePlanMember to ions_EmployeeStockPurchasePlanMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EmployeeStockPurchasePlanMember_lbl1" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanMember_lbl1">Employee Stock Purchase Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanMember" xlink:to="ions_EmployeeStockPurchasePlanMember_lbl1" xlink:title="label: EmployeeStockPurchasePlanMember to ions_EmployeeStockPurchasePlanMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EmployeeStockPurchasePlanMember" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanMember">Employee Stock Purchase Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanMember" xlink:to="ions_EmployeeStockPurchasePlanMember" xlink:title="label: EmployeeStockPurchasePlanMember to ions_EmployeeStockPurchasePlanMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" xlink:label="IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" xlink:title="IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl">Increase (decrease) in the number of shares in the "fungible" share reserve for each share issued pursuant to full value award.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl1" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl1">Increase (decrease) in fungible share reserve for each share issued pursuant to full value award</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward">Reduction in fungible share reserve for each share issued pursuant to full value award (n shares)</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward" xlink:label="IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward" xlink:title="IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl">Increase (decrease) in the number of shares in the "fungible" share reserve for each share of common stock returning from a full value award.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl1" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl1">Increase (decrease) in fungible share reserve for each share returning from full value award</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward">Increase in fungible share reserve for each share returning from a full value award (in shares)</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LesseeOperatingLeaseInformationTableTextBlock" xlink:label="LesseeOperatingLeaseInformationTableTextBlock" xlink:title="LesseeOperatingLeaseInformationTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl">Tabular disclosure of information on lessee's operating leases, including carrying value of right-of-use assets and lease liabilities, weighted-average remaining term and weighted-average discount rate.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInformationTableTextBlock" xlink:to="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" xlink:title="label: LesseeOperatingLeaseInformationTableTextBlock to ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1">Lessee, Operating Lease Information [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInformationTableTextBlock" xlink:to="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" xlink:title="label: LesseeOperatingLeaseInformationTableTextBlock to ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInformationTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseInformationTableTextBlock" xml:lang="en-US" id="ions_LesseeOperatingLeaseInformationTableTextBlock">Amounts Related to Operating Leases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInformationTableTextBlock" xlink:to="ions_LesseeOperatingLeaseInformationTableTextBlock" xlink:title="label: LesseeOperatingLeaseInformationTableTextBlock to ions_LesseeOperatingLeaseInformationTableTextBlock" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ConvertibleNotesDisclosureTable" xlink:label="ConvertibleNotesDisclosureTable" xlink:title="ConvertibleNotesDisclosureTable" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureTable_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleNotesDisclosureTable_lbl" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureTable_lbl">Disclosure of information about income taxes.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureTable" xlink:to="ions_ConvertibleNotesDisclosureTable_lbl" xlink:title="label: ConvertibleNotesDisclosureTable to ions_ConvertibleNotesDisclosureTable_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleNotesDisclosureTable_lbl1" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureTable_lbl1">Convertible Notes Disclosure [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureTable" xlink:to="ions_ConvertibleNotesDisclosureTable_lbl1" xlink:title="label: ConvertibleNotesDisclosureTable to ions_ConvertibleNotesDisclosureTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ConvertibleNotesDisclosureLineItems" xlink:label="ConvertibleNotesDisclosureLineItems" xlink:title="ConvertibleNotesDisclosureLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleNotesDisclosureLineItems_lbl" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureLineItems_lbl">Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureLineItems" xlink:to="ions_ConvertibleNotesDisclosureLineItems_lbl" xlink:title="label: ConvertibleNotesDisclosureLineItems to ions_ConvertibleNotesDisclosureLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleNotesDisclosureLineItems_lbl1" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureLineItems_lbl1">Convertible Notes Disclosure [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureLineItems" xlink:to="ions_ConvertibleNotesDisclosureLineItems_lbl1" xlink:title="label: ConvertibleNotesDisclosureLineItems to ions_ConvertibleNotesDisclosureLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureLineItems" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleNotesDisclosureLineItems" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureLineItems">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureLineItems" xlink:to="ions_ConvertibleNotesDisclosureLineItems" xlink:title="label: ConvertibleNotesDisclosureLineItems to ions_ConvertibleNotesDisclosureLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PropertyPlantAndEquipmentUsefulLivesTableTextBlock" xlink:label="PropertyPlantAndEquipmentUsefulLivesTableTextBlock" xlink:title="PropertyPlantAndEquipmentUsefulLivesTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="ions_PropertyPlantAndEquipmentUsefulLivesTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PropertyPlantAndEquipmentUsefulLivesTableTextBlock_lbl" xml:lang="en-US" id="ions_PropertyPlantAndEquipmentUsefulLivesTableTextBlock_lbl">Tabular disclosure of the useful lives of physical assets used in the normal conduct of business and not intended for resale.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_PropertyPlantAndEquipmentUsefulLivesTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PropertyPlantAndEquipmentUsefulLivesTableTextBlock_lbl1" xml:lang="en-US" id="ions_PropertyPlantAndEquipmentUsefulLivesTableTextBlock_lbl1">Property, Plant and Equipment Useful Lives [Table Text Block]</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_PropertyPlantAndEquipmentUsefulLivesTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PropertyPlantAndEquipmentUsefulLivesTableTextBlock" xml:lang="en-US" id="ions_PropertyPlantAndEquipmentUsefulLivesTableTextBlock">Property, Plant and Equipment</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PatentExpenses" xlink:label="PatentExpenses" xlink:title="PatentExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_PatentExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PatentExpenses_lbl" xml:lang="en-US" id="ions_PatentExpenses_lbl">Includes charges for amortization and write-downs of capitalized patent costs as well as legal fees for patent litigation and patent defense.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_PatentExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PatentExpenses_lbl1" xml:lang="en-US" id="ions_PatentExpenses_lbl1">Patent Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PatentExpenses" xlink:to="ions_PatentExpenses_lbl1" xlink:title="label: PatentExpenses to ions_PatentExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PatentExpenses" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PatentExpenses" xml:lang="en-US" id="ions_PatentExpenses">Patent expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PatentExpenses" xlink:to="ions_PatentExpenses" xlink:title="label: PatentExpenses to ions_PatentExpenses" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" />
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    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent">Gross unrealized gains</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" xlink:label="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" xlink:title="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl">Amount, before tax, of unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl1">Debt Securities, Available-for-sale, Accumulated Gross Unrealized Gain, before Tax, Noncurrent</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent">Gross unrealized gains</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" xlink:label="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" xlink:title="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent_lbl" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent_lbl">Amount, before tax, of unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent_lbl1">Debt Securities, Available-for-sale, Accumulated Gross Unrealized Loss, before Tax, Noncurrent</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent">Gross unrealized losses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" xlink:to="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" xlink:title="label: DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent to ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" xlink:label="EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" xlink:title="EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl" xml:lang="en-US" id="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl">Accumulated amount of unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:label="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:title="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl" xml:lang="en-US" id="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl">Accumulated amount of unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:to="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:title="label: EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss to ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumContractMaturityPeriodRange2" xlink:label="MaximumContractMaturityPeriodRange2" xlink:title="MaximumContractMaturityPeriodRange2" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl">The maximum contract maturity period for the second range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl1">Maximum contract maturity period, range 2</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange2" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2">Maximum contract maturity period, range 2</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumContractMaturityPeriodRange1" xlink:label="MaximumContractMaturityPeriodRange1" xlink:title="MaximumContractMaturityPeriodRange1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl">The maximum contract maturity period for the first range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl1">Maximum contract maturity period, range 1</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1">Maximum contract maturity period, range 1</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange1" xlink:to="ions_MaximumContractMaturityPeriodRange1" xlink:title="label: MaximumContractMaturityPeriodRange1 to ions_MaximumContractMaturityPeriodRange1" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumContractMaturityPeriodRange3" xlink:label="MaximumContractMaturityPeriodRange3" xlink:title="MaximumContractMaturityPeriodRange3" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange3_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3_lbl">The maximum contract maturity period for the third range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange3_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3_lbl1">Maximum contract maturity period, range 3</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange3" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3">Maximum contract maturity period, range 3</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" />
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature within two years of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage">Percentage of available-for-sale securities with a maturity of less than two years</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl">The aggregate percentage of all available-for-sale debt securities, regardless of maturity.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage">Total</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl">The percentage of available-for-sale debt securities that mature within one year of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage">One year or less</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature beyond one year but within two years of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, after One Through Two Years, Percentage</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:label="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:title="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" xml:lang="en-US" id="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl">Collaboration agreement entered into with AstraZeneca PLC in July 2015 to discover and develop antisense therapies for treating cardiovascular and metabolic diseases primarily focused on targets in the kidney and renal diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:to="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" xlink:title="label: AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember to ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:to="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:title="label: AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember to ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AstraZenecaCollaborationWainuaMember" xlink:label="AstraZenecaCollaborationWainuaMember" xlink:title="AstraZenecaCollaborationWainuaMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstraZenecaCollaborationWainuaMember_lbl" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember_lbl">Collaboration agreement entered into with AstraZeneca PLC in December 2021 to develop and commercialize WAINUA. WAINUA (eplontersen), formerly known as IONIS-TTR-L and AKCEA-TTR-L, is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce the production of transthyretin, or TTR protein, to treat all types of TTR amyloidosis (ATTR), a systemic, progressive and fatal disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember_lbl" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstraZenecaCollaborationWainuaMember_lbl1" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember_lbl1">AstraZeneca Collaboration, WAINUA [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_AstraZenecaCollaborationWainuaMember" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember">WAINUA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember_lbl2" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_Ion826Member" xlink:label="Ion826Member" xlink:title="Ion826Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion826Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion826Member_lbl" xml:lang="en-US" id="ions_Ion826Member_lbl">ION826 is a medicine designed for the treatment of heart failure.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_Ion826Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion826Member_lbl1" xml:lang="en-US" id="ions_Ion826Member_lbl1">Ion826 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion826Member" xlink:to="ions_Ion826Member_lbl1" xlink:title="label: Ion826Member to ions_Ion826Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion826Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion826Member" xml:lang="en-US" id="ions_Ion826Member">ION826 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion826Member" xlink:to="ions_Ion826Member" xlink:title="label: Ion826Member to ions_Ion826Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DebtInstrumentNumberOfConvertibleNotes" xlink:label="DebtInstrumentNumberOfConvertibleNotes" xlink:title="DebtInstrumentNumberOfConvertibleNotes" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentNumberOfConvertibleNotes_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentNumberOfConvertibleNotes_lbl" xml:lang="en-US" id="ions_DebtInstrumentNumberOfConvertibleNotes_lbl">Number of outstanding convertible notes.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNumberOfConvertibleNotes" xlink:to="ions_DebtInstrumentNumberOfConvertibleNotes_lbl" xlink:title="label: DebtInstrumentNumberOfConvertibleNotes to ions_DebtInstrumentNumberOfConvertibleNotes_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentNumberOfConvertibleNotes_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentNumberOfConvertibleNotes_lbl1" xml:lang="en-US" id="ions_DebtInstrumentNumberOfConvertibleNotes_lbl1">Debt Instrument, Number of convertible notes</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentNumberOfConvertibleNotes" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentNumberOfConvertibleNotes" xml:lang="en-US" id="ions_DebtInstrumentNumberOfConvertibleNotes">Number of outstanding convertible notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNumberOfConvertibleNotes" xlink:to="ions_DebtInstrumentNumberOfConvertibleNotes" xlink:title="label: DebtInstrumentNumberOfConvertibleNotes to ions_DebtInstrumentNumberOfConvertibleNotes" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_OtsukaCollaborationsMember" xlink:label="OtsukaCollaborationsMember" xlink:title="OtsukaCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtsukaCollaborationsMember_lbl" xml:lang="en-US" id="ions_OtsukaCollaborationsMember_lbl">Collaboration agreements entered into with Otsuka Pharmaceutical Co., Ltd.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaCollaborationsMember" xlink:to="ions_OtsukaCollaborationsMember_lbl" xlink:title="label: OtsukaCollaborationsMember to ions_OtsukaCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtsukaCollaborationsMember_lbl1" xml:lang="en-US" id="ions_OtsukaCollaborationsMember_lbl1">Otsuka Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaCollaborationsMember" xlink:to="ions_OtsukaCollaborationsMember_lbl1" xlink:title="label: OtsukaCollaborationsMember to ions_OtsukaCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaCollaborationsMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OtsukaCollaborationsMember" xml:lang="en-US" id="ions_OtsukaCollaborationsMember">Otsuka [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaCollaborationsMember" xlink:to="ions_OtsukaCollaborationsMember" xlink:title="label: OtsukaCollaborationsMember to ions_OtsukaCollaborationsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AlnylamPharmaceuticalsIncMember" xlink:label="AlnylamPharmaceuticalsIncMember" xlink:title="AlnylamPharmaceuticalsIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamPharmaceuticalsIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AlnylamPharmaceuticalsIncMember_lbl" xml:lang="en-US" id="ions_AlnylamPharmaceuticalsIncMember_lbl">Represents activity related to Alnylam Pharmaceuticals, Inc..</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamPharmaceuticalsIncMember" xlink:to="ions_AlnylamPharmaceuticalsIncMember_lbl" xlink:title="label: AlnylamPharmaceuticalsIncMember to ions_AlnylamPharmaceuticalsIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamPharmaceuticalsIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AlnylamPharmaceuticalsIncMember_lbl1" xml:lang="en-US" id="ions_AlnylamPharmaceuticalsIncMember_lbl1">Alnylam Pharmaceuticals, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamPharmaceuticalsIncMember" xlink:to="ions_AlnylamPharmaceuticalsIncMember_lbl1" xlink:title="label: AlnylamPharmaceuticalsIncMember to ions_AlnylamPharmaceuticalsIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamPharmaceuticalsIncMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AlnylamPharmaceuticalsIncMember" xml:lang="en-US" id="ions_AlnylamPharmaceuticalsIncMember">Alnylam [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamPharmaceuticalsIncMember" xlink:to="ions_AlnylamPharmaceuticalsIncMember" xlink:title="label: AlnylamPharmaceuticalsIncMember to ions_AlnylamPharmaceuticalsIncMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl">Disclosure of information about collaborative arrangements and non-collaborative arrangement transactions.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1">Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl">Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1">Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems">Collaborative Arrangements and Licensing Agreements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NovartisCollaborationMember" xlink:label="NovartisCollaborationMember" xlink:title="NovartisCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NovartisCollaborationMember_lbl" xml:lang="en-US" id="ions_NovartisCollaborationMember_lbl">Collaboration agreement entered into with Novartis International AG (Novartis) in January 2017 to develop and commercialize pelacarsen and olezarsen.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationMember" xlink:to="ions_NovartisCollaborationMember_lbl" xlink:title="label: NovartisCollaborationMember to ions_NovartisCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NovartisCollaborationMember_lbl1" xml:lang="en-US" id="ions_NovartisCollaborationMember_lbl1">Novartis Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationMember" xlink:to="ions_NovartisCollaborationMember_lbl1" xlink:title="label: NovartisCollaborationMember to ions_NovartisCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NovartisCollaborationMember" xml:lang="en-US" id="ions_NovartisCollaborationMember">Novartis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationMember" xlink:to="ions_NovartisCollaborationMember" xlink:title="label: NovartisCollaborationMember to ions_NovartisCollaborationMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_GlaxoSmithKlineCollaborationMember" xlink:label="GlaxoSmithKlineCollaborationMember" xlink:title="GlaxoSmithKlineCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_GlaxoSmithKlineCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GlaxoSmithKlineCollaborationMember_lbl" xml:lang="en-US" id="ions_GlaxoSmithKlineCollaborationMember_lbl">Collaboration agreement entered into with GlaxoSmithKline (GSK) in March 2010 to discover and develop new medicines against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GlaxoSmithKlineCollaborationMember" xlink:to="ions_GlaxoSmithKlineCollaborationMember_lbl" xlink:title="label: GlaxoSmithKlineCollaborationMember to ions_GlaxoSmithKlineCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GlaxoSmithKlineCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GlaxoSmithKlineCollaborationMember_lbl1" xml:lang="en-US" id="ions_GlaxoSmithKlineCollaborationMember_lbl1">Glaxo Smith Kline Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GlaxoSmithKlineCollaborationMember" xlink:to="ions_GlaxoSmithKlineCollaborationMember_lbl1" xlink:title="label: GlaxoSmithKlineCollaborationMember to ions_GlaxoSmithKlineCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GlaxoSmithKlineCollaborationMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GlaxoSmithKlineCollaborationMember" xml:lang="en-US" id="ions_GlaxoSmithKlineCollaborationMember">GSK [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GlaxoSmithKlineCollaborationMember" xlink:to="ions_GlaxoSmithKlineCollaborationMember" xlink:title="label: GlaxoSmithKlineCollaborationMember to ions_GlaxoSmithKlineCollaborationMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RocheCollaborationsMember" xlink:label="RocheCollaborationsMember" xlink:title="RocheCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationsMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationsMember_lbl">Collaboration agreements entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationsMember" xlink:to="ions_RocheCollaborationsMember_lbl" xlink:title="label: RocheCollaborationsMember to ions_RocheCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RocheCollaborationsMember_lbl1" xml:lang="en-US" id="ions_RocheCollaborationsMember_lbl1">Roche Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationsMember" xlink:to="ions_RocheCollaborationsMember_lbl1" xlink:title="label: RocheCollaborationsMember to ions_RocheCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationsMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RocheCollaborationsMember" xml:lang="en-US" id="ions_RocheCollaborationsMember">Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationsMember" xlink:to="ions_RocheCollaborationsMember" xlink:title="label: RocheCollaborationsMember to ions_RocheCollaborationsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_BiogenCollaborationsMember" xlink:label="BiogenCollaborationsMember" xlink:title="BiogenCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaborationsMember_lbl" xml:lang="en-US" id="ions_BiogenCollaborationsMember_lbl">Collaboration agreements entered into with Biogen Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember_lbl" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaborationsMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaborationsMember_lbl1">Biogen Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember_lbl1" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaborationsMember" xml:lang="en-US" id="ions_BiogenCollaborationsMember">Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AstrazenecaCollaborationsMember" xlink:label="AstrazenecaCollaborationsMember" xlink:title="AstrazenecaCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstrazenecaCollaborationsMember_lbl" xml:lang="en-US" id="ions_AstrazenecaCollaborationsMember_lbl">Collaboration agreements entered into with AstraZeneca PLC.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationsMember" xlink:to="ions_AstrazenecaCollaborationsMember_lbl" xlink:title="label: AstrazenecaCollaborationsMember to ions_AstrazenecaCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstrazenecaCollaborationsMember_lbl1" xml:lang="en-US" id="ions_AstrazenecaCollaborationsMember_lbl1">AstraZeneca Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationsMember" xlink:to="ions_AstrazenecaCollaborationsMember_lbl1" xlink:title="label: AstrazenecaCollaborationsMember to ions_AstrazenecaCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationsMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AstrazenecaCollaborationsMember" xml:lang="en-US" id="ions_AstrazenecaCollaborationsMember">AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationsMember" xlink:to="ions_AstrazenecaCollaborationsMember" xlink:title="label: AstrazenecaCollaborationsMember to ions_AstrazenecaCollaborationsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RevenueFromContractWithCustomerTransactionPrice" xlink:label="RevenueFromContractWithCustomerTransactionPrice" xlink:title="RevenueFromContractWithCustomerTransactionPrice" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice_lbl">The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1">Revenue from Contract with Customer, Transaction Price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice">Transaction price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:label="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:title="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl">The number of separate performance obligations under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1">Revenue from Contract with Customer, Number of separate performance obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">Number of separate performance obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:label="MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:title="MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl">The maximum amount of milestone payments to be received for each medicine that is successfully developed over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1">Maximum amount of milestone payments per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration">Maximum amount of milestone payments for each additional medicine successfully developed over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:title="label: MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfMedicine" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl">Royalty percentage received on the net sales of a medicine by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfMedicine to ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1">Royalty percentage received on net sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfMedicine to ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine">Royalty percentage received on net sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfMedicine to ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CumulativePaymentsReceived" xlink:label="CumulativePaymentsReceived" xlink:title="CumulativePaymentsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CumulativePaymentsReceived_lbl" xml:lang="en-US" id="ions_CumulativePaymentsReceived_lbl">Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived_lbl" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CumulativePaymentsReceived_lbl1" xml:lang="en-US" id="ions_CumulativePaymentsReceived_lbl1">Cumulative payments received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived_lbl1" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CumulativePaymentsReceived" xml:lang="en-US" id="ions_CumulativePaymentsReceived">Cumulative payments received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfEarlyStagePrograms" xlink:label="NumberOfEarlyStagePrograms" xlink:title="NumberOfEarlyStagePrograms" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfEarlyStagePrograms_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfEarlyStagePrograms_lbl" xml:lang="en-US" id="ions_NumberOfEarlyStagePrograms_lbl">Number of early-stage programs to be developed for RNA-targeting investigational medicines for the treatment of Alzheimer's disease (AD) and Huntington's disease (HD).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfEarlyStagePrograms" xlink:to="ions_NumberOfEarlyStagePrograms_lbl" xlink:title="label: NumberOfEarlyStagePrograms to ions_NumberOfEarlyStagePrograms_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfEarlyStagePrograms_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfEarlyStagePrograms_lbl1" xml:lang="en-US" id="ions_NumberOfEarlyStagePrograms_lbl1">Number of early-stage programs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfEarlyStagePrograms" xlink:to="ions_NumberOfEarlyStagePrograms_lbl1" xlink:title="label: NumberOfEarlyStagePrograms to ions_NumberOfEarlyStagePrograms_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl">The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1">Maximum amount of regulatory milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">Maximum amount of regulatory milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl">The maximum amount of upfront payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration to ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1">Maximum amount of upfront payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration to ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration">Maximum amount of upfront payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:title="label: MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration to ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:label="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:title="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl">The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1">Maximum amount of payments receivable over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">Maximum amount of payments receivable over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:title="label: MaximumAmountOfPaymentsReceivableOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl">The maximum amount of development milestone payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1">Maximum amount of development milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">Maximum amount of development milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:label="MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:title="MaximumAmountOfLicenseFeesOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl">The maximum amount of license fees to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfLicenseFeesOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl1">Maximum amount of license fees over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfLicenseFeesOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration">Maximum amount of license fees over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:title="label: MaximumAmountOfLicenseFeesOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NextPaymentToBeAchieved" xlink:label="NextPaymentToBeAchieved" xlink:title="NextPaymentToBeAchieved" />
    <link:label xlink:type="resource" xlink:label="ions_NextPaymentToBeAchieved_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NextPaymentToBeAchieved_lbl" xml:lang="en-US" id="ions_NextPaymentToBeAchieved_lbl">The next payment to be achieved under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPaymentToBeAchieved" xlink:to="ions_NextPaymentToBeAchieved_lbl" xlink:title="label: NextPaymentToBeAchieved to ions_NextPaymentToBeAchieved_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NextPaymentToBeAchieved_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NextPaymentToBeAchieved_lbl1" xml:lang="en-US" id="ions_NextPaymentToBeAchieved_lbl1">Next payment to be achieved</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPaymentToBeAchieved" xlink:to="ions_NextPaymentToBeAchieved_lbl1" xlink:title="label: NextPaymentToBeAchieved to ions_NextPaymentToBeAchieved_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NextPaymentToBeAchieved" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NextPaymentToBeAchieved" xml:lang="en-US" id="ions_NextPaymentToBeAchieved">Next payment to be achieved</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPaymentToBeAchieved" xlink:to="ions_NextPaymentToBeAchieved" xlink:title="label: NextPaymentToBeAchieved to ions_NextPaymentToBeAchieved" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl">The maximum amount of sales milestone payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" />
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember" xlink:label="ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember" xlink:title="ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl">Research and development (R&amp;D) services for the investigational medicine for Huntington's Disease (HD).</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:label="CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:title="CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" xml:lang="en-US" id="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl">Cumulative payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" xlink:label="ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" xlink:title="ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" />
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    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl1">Research and Development Services for Investigational Medicine for Alzheimer's Disease [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember">R&amp;D Services for Investigational Medicine for AD [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" xlink:to="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" xlink:title="label: ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember to ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RocheCollaborationRNATargetedProgramsForADAndHDMember" xlink:label="RocheCollaborationRNATargetedProgramsForADAndHDMember" xlink:title="RocheCollaborationRNATargetedProgramsForADAndHDMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl">Collaboration agreement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in September 2023 to develop two undisclosed early-stage programs for RNA-targeting investigational medicines for the treatment of Alzheimer's disease (AD) and Huntington's disease (HD).</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_UpfrontPaymentReceived" xlink:label="UpfrontPaymentReceived" xlink:title="UpfrontPaymentReceived" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontPaymentReceived_lbl" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl">The amount of upfront payments received during the period under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontPaymentReceived_lbl1" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl1">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl1" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontPaymentReceived" xml:lang="en-US" id="ions_UpfrontPaymentReceived">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:label="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:title="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl">Collaboration agreement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in October 2018 to develop IONIS-FB-L for the treatment of complement-mediated diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1">Roche Collaboration, Ionis-Fb-L for Complement-Mediated Diseases [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember">Sefaxersen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RocheCollaborationHuntingtonsDiseaseMember" xlink:label="RocheCollaborationHuntingtonsDiseaseMember" xlink:title="RocheCollaborationHuntingtonsDiseaseMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl">Collaboration agreement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in April 2013 to develop treatments for Huntington's disease, or HD, based on the Company's antisense technology.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationHuntingtonsDiseaseMember" xlink:to="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" xlink:title="label: RocheCollaborationHuntingtonsDiseaseMember to ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" xml:lang="en-US" id="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1">Roche Collaboration, Huntington's Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationHuntingtonsDiseaseMember" xlink:to="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" xlink:title="label: RocheCollaborationHuntingtonsDiseaseMember to ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationHuntingtonsDiseaseMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RocheCollaborationHuntingtonsDiseaseMember" xml:lang="en-US" id="ions_RocheCollaborationHuntingtonsDiseaseMember">HD [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationHuntingtonsDiseaseMember" xlink:to="ions_RocheCollaborationHuntingtonsDiseaseMember" xlink:title="label: RocheCollaborationHuntingtonsDiseaseMember to ions_RocheCollaborationHuntingtonsDiseaseMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_IonisMaptMember" xlink:label="IonisMaptMember" xlink:title="IonisMaptMember" />
    <link:label xlink:type="resource" xlink:label="ions_IonisMaptMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisMaptMember_lbl" xml:lang="en-US" id="ions_IonisMaptMember_lbl">IONIS-MAPT is an antisense drug designed to selectively reduce the production of microtubule-associated protein tau (MAPT), or tau protein, in the brain, for the treatment of Alzheimer's disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisMaptMember" xlink:to="ions_IonisMaptMember_lbl" xlink:title="label: IonisMaptMember to ions_IonisMaptMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IonisMaptMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IonisMaptMember_lbl1" xml:lang="en-US" id="ions_IonisMaptMember_lbl1">Ionis-Mapt [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisMaptMember" xlink:to="ions_IonisMaptMember_lbl1" xlink:title="label: IonisMaptMember to ions_IonisMaptMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IonisMaptMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IonisMaptMember" xml:lang="en-US" id="ions_IonisMaptMember">IONIS-MAPT [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisMaptMember" xlink:to="ions_IonisMaptMember" xlink:title="label: IonisMaptMember to ions_IonisMaptMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_QalsodyResearchAndDevelopmentMember" xlink:label="QalsodyResearchAndDevelopmentMember" xlink:title="QalsodyResearchAndDevelopmentMember" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyResearchAndDevelopmentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_QalsodyResearchAndDevelopmentMember_lbl" xml:lang="en-US" id="ions_QalsodyResearchAndDevelopmentMember_lbl">Research and development revenue from QALSODY.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyResearchAndDevelopmentMember" xlink:to="ions_QalsodyResearchAndDevelopmentMember_lbl" xlink:title="label: QalsodyResearchAndDevelopmentMember to ions_QalsodyResearchAndDevelopmentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyResearchAndDevelopmentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_QalsodyResearchAndDevelopmentMember_lbl1" xml:lang="en-US" id="ions_QalsodyResearchAndDevelopmentMember_lbl1">QALSODY Research and Development [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyResearchAndDevelopmentMember" xlink:to="ions_QalsodyResearchAndDevelopmentMember_lbl1" xlink:title="label: QalsodyResearchAndDevelopmentMember to ions_QalsodyResearchAndDevelopmentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyResearchAndDevelopmentMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_QalsodyResearchAndDevelopmentMember" xml:lang="en-US" id="ions_QalsodyResearchAndDevelopmentMember">QALSODY R&amp;D Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyResearchAndDevelopmentMember" xlink:to="ions_QalsodyResearchAndDevelopmentMember" xlink:title="label: QalsodyResearchAndDevelopmentMember to ions_QalsodyResearchAndDevelopmentMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_QalsodyRoyaltiesMember" xlink:label="QalsodyRoyaltiesMember" xlink:title="QalsodyRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyRoyaltiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_QalsodyRoyaltiesMember_lbl" xml:lang="en-US" id="ions_QalsodyRoyaltiesMember_lbl">Royalty revenues from the sale of QALSODY.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyRoyaltiesMember" xlink:to="ions_QalsodyRoyaltiesMember_lbl" xlink:title="label: QalsodyRoyaltiesMember to ions_QalsodyRoyaltiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_QalsodyRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_QalsodyRoyaltiesMember_lbl1">QALSODY Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyRoyaltiesMember" xlink:to="ions_QalsodyRoyaltiesMember_lbl1" xlink:title="label: QalsodyRoyaltiesMember to ions_QalsodyRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyRoyaltiesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_QalsodyRoyaltiesMember" xml:lang="en-US" id="ions_QalsodyRoyaltiesMember">QALSODY Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyRoyaltiesMember" xlink:to="ions_QalsodyRoyaltiesMember" xlink:title="label: QalsodyRoyaltiesMember to ions_QalsodyRoyaltiesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_Ion306Member" xlink:label="Ion306Member" xlink:title="Ion306Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion306Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion306Member_lbl" xml:lang="en-US" id="ions_Ion306Member_lbl">ION306 is an antisense oligonucleotide or ASO that is designed to boost production of the survival motor neuron protein, known as SMN.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion306Member" xlink:to="ions_Ion306Member_lbl" xlink:title="label: Ion306Member to ions_Ion306Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion306Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion306Member_lbl1" xml:lang="en-US" id="ions_Ion306Member_lbl1">Ion306 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion306Member" xlink:to="ions_Ion306Member_lbl1" xlink:title="label: Ion306Member to ions_Ion306Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion306Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion306Member" xml:lang="en-US" id="ions_Ion306Member">ION306 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion306Member" xlink:to="ions_Ion306Member" xlink:title="label: Ion306Member to ions_Ion306Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:label="MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:title="MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl">The maximum amount of development milestone payments to be received for each medicine that achieves marketing approval over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1">Maximum amount of development milestone payments per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration">Maximum amount of development milestone payments per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:label="MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:title="MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl">The maximum amount of regulatory milestone payments to be received for each medicine that achieves marketing approval over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1">Maximum amount of regulatory milestone payments per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration">Maximum amount of regulatory milestone payments per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:label="MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:title="MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl">The maximum amount of license fees to be received for each medicine that achieves marketing approval over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl1">Maximum amount of license fees per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration">Maximum amount of license fees per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:title="label: MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_QalsodyMember" xlink:label="QalsodyMember" xlink:title="QalsodyMember" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_QalsodyMember_lbl" xml:lang="en-US" id="ions_QalsodyMember_lbl">Tofersen (IONIS-SOD1Rx or BIIB067), or QALSODY, is an antisense medicine designed to inhibit the production of superoxide dismutase 1, or SOD1, which is a well understood genetic cause of familial amyotrophic lateral sclerosis, or ALS.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyMember" xlink:to="ions_QalsodyMember_lbl" xlink:title="label: QalsodyMember to ions_QalsodyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_QalsodyMember_lbl1" xml:lang="en-US" id="ions_QalsodyMember_lbl1">QALSODY [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyMember" xlink:to="ions_QalsodyMember_lbl1" xlink:title="label: QalsodyMember to ions_QalsodyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_QalsodyMember" xml:lang="en-US" id="ions_QalsodyMember">QALSODY [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyMember" xlink:to="ions_QalsodyMember" xlink:title="label: QalsodyMember to ions_QalsodyMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:label="MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:title="MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl">The maximum amount of payments the Company is eligible to receive for each medicine that achieves marketing approval over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl1">Maximum amount of payments receivable per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration">Maximum amount of payments receivable per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:title="label: MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_Ion582Member" xlink:label="Ion582Member" xlink:title="Ion582Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion582Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion582Member_lbl" xml:lang="en-US" id="ions_Ion582Member_lbl">ION582 is an antisense investigational medicine that targets Ubiquitin Protein Ligase E3A-Antisense Transcript (UBE3A-ATS), which is a long non-coding ribonucleic acid (lncRNA).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion582Member" xlink:to="ions_Ion582Member_lbl" xlink:title="label: Ion582Member to ions_Ion582Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion582Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion582Member_lbl1" xml:lang="en-US" id="ions_Ion582Member_lbl1">ION582 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion582Member" xlink:to="ions_Ion582Member_lbl1" xlink:title="label: Ion582Member to ions_Ion582Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion582Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion582Member" xml:lang="en-US" id="ions_Ion582Member">ION582 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion582Member" xlink:to="ions_Ion582Member" xlink:title="label: Ion582Member to ions_Ion582Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PremiumPaidOnSharesPurchased" xlink:label="PremiumPaidOnSharesPurchased" xlink:title="PremiumPaidOnSharesPurchased" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumPaidOnSharesPurchased_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PremiumPaidOnSharesPurchased_lbl" xml:lang="en-US" id="ions_PremiumPaidOnSharesPurchased_lbl">The cash premium paid on the purchase of the Company's common stock under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumPaidOnSharesPurchased" xlink:to="ions_PremiumPaidOnSharesPurchased_lbl" xlink:title="label: PremiumPaidOnSharesPurchased to ions_PremiumPaidOnSharesPurchased_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumPaidOnSharesPurchased_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PremiumPaidOnSharesPurchased_lbl1" xml:lang="en-US" id="ions_PremiumPaidOnSharesPurchased_lbl1">Premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumPaidOnSharesPurchased" xlink:to="ions_PremiumPaidOnSharesPurchased_lbl1" xlink:title="label: PremiumPaidOnSharesPurchased to ions_PremiumPaidOnSharesPurchased_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumPaidOnSharesPurchased" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PremiumPaidOnSharesPurchased" xml:lang="en-US" id="ions_PremiumPaidOnSharesPurchased">Premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumPaidOnSharesPurchased" xlink:to="ions_PremiumPaidOnSharesPurchased" xlink:title="label: PremiumPaidOnSharesPurchased to ions_PremiumPaidOnSharesPurchased" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_SpinrazaResearchAndDevelopmentMember" xlink:label="SpinrazaResearchAndDevelopmentMember" xlink:title="SpinrazaResearchAndDevelopmentMember" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaResearchAndDevelopmentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SpinrazaResearchAndDevelopmentMember_lbl" xml:lang="en-US" id="ions_SpinrazaResearchAndDevelopmentMember_lbl">Research and development revenue from SPINRAZA (nusinersen).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaResearchAndDevelopmentMember" xlink:to="ions_SpinrazaResearchAndDevelopmentMember_lbl" xlink:title="label: SpinrazaResearchAndDevelopmentMember to ions_SpinrazaResearchAndDevelopmentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaResearchAndDevelopmentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SpinrazaResearchAndDevelopmentMember_lbl1" xml:lang="en-US" id="ions_SpinrazaResearchAndDevelopmentMember_lbl1">SPINRAZA Research and Development [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaResearchAndDevelopmentMember" xlink:to="ions_SpinrazaResearchAndDevelopmentMember_lbl1" xlink:title="label: SpinrazaResearchAndDevelopmentMember to ions_SpinrazaResearchAndDevelopmentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaResearchAndDevelopmentMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SpinrazaResearchAndDevelopmentMember" xml:lang="en-US" id="ions_SpinrazaResearchAndDevelopmentMember">SPINRAZA R&amp;D Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaResearchAndDevelopmentMember" xlink:to="ions_SpinrazaResearchAndDevelopmentMember" xlink:title="label: SpinrazaResearchAndDevelopmentMember to ions_SpinrazaResearchAndDevelopmentMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_BiogenCollaboration2012NeurologyMember" xlink:label="BiogenCollaboration2012NeurologyMember" xlink:title="BiogenCollaboration2012NeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2012NeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaboration2012NeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaboration2012NeurologyMember_lbl">Collaborative agreement entered into with Biogen Inc. in December 2012 focused on developing and commercializing novel antisense drugs for up to three targets to treat neurological or neuromuscular diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2012NeurologyMember" xlink:to="ions_BiogenCollaboration2012NeurologyMember_lbl" xlink:title="label: BiogenCollaboration2012NeurologyMember to ions_BiogenCollaboration2012NeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2012NeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaboration2012NeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaboration2012NeurologyMember_lbl1">Biogen Collaboration, 2012 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2012NeurologyMember" xlink:to="ions_BiogenCollaboration2012NeurologyMember_lbl1" xlink:title="label: BiogenCollaboration2012NeurologyMember to ions_BiogenCollaboration2012NeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2012NeurologyMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaboration2012NeurologyMember" xml:lang="en-US" id="ions_BiogenCollaboration2012NeurologyMember">2012 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2012NeurologyMember" xlink:to="ions_BiogenCollaboration2012NeurologyMember" xlink:title="label: BiogenCollaboration2012NeurologyMember to ions_BiogenCollaboration2012NeurologyMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_BiogenCollaboration2018NeurologyMember" xlink:label="BiogenCollaboration2018NeurologyMember" xlink:title="BiogenCollaboration2018NeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2018NeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaboration2018NeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaboration2018NeurologyMember_lbl">Collaboration agreement entered into with Biogen Inc. in April 2018 to develop novel antisense drug candidates for a broad range of neurological diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2018NeurologyMember" xlink:to="ions_BiogenCollaboration2018NeurologyMember_lbl" xlink:title="label: BiogenCollaboration2018NeurologyMember to ions_BiogenCollaboration2018NeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2018NeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaboration2018NeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaboration2018NeurologyMember_lbl1">Biogen Collaboration, 2018 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2018NeurologyMember" xlink:to="ions_BiogenCollaboration2018NeurologyMember_lbl1" xlink:title="label: BiogenCollaboration2018NeurologyMember to ions_BiogenCollaboration2018NeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2018NeurologyMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaboration2018NeurologyMember" xml:lang="en-US" id="ions_BiogenCollaboration2018NeurologyMember">2018 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2018NeurologyMember" xlink:to="ions_BiogenCollaboration2018NeurologyMember" xlink:title="label: BiogenCollaboration2018NeurologyMember to ions_BiogenCollaboration2018NeurologyMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_BiogenCollaboration2013NeurologyMember" xlink:label="BiogenCollaboration2013NeurologyMember" xlink:title="BiogenCollaboration2013NeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013NeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaboration2013NeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaboration2013NeurologyMember_lbl">Collaborative agreement entered into with Biogen Inc. in September 2013 focused on applying antisense technology to advance the treatment of neurodegenerative diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013NeurologyMember" xlink:to="ions_BiogenCollaboration2013NeurologyMember_lbl" xlink:title="label: BiogenCollaboration2013NeurologyMember to ions_BiogenCollaboration2013NeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013NeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaboration2013NeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaboration2013NeurologyMember_lbl1">Biogen Collaboration, 2013 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013NeurologyMember" xlink:to="ions_BiogenCollaboration2013NeurologyMember_lbl1" xlink:title="label: BiogenCollaboration2013NeurologyMember to ions_BiogenCollaboration2013NeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013NeurologyMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaboration2013NeurologyMember" xml:lang="en-US" id="ions_BiogenCollaboration2013NeurologyMember">2013 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013NeurologyMember" xlink:to="ions_BiogenCollaboration2013NeurologyMember" xlink:title="label: BiogenCollaboration2013NeurologyMember to ions_BiogenCollaboration2013NeurologyMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_BiogenCollaborationSpinrazaMember" xlink:label="BiogenCollaborationSpinrazaMember" xlink:title="BiogenCollaborationSpinrazaMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationSpinrazaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaborationSpinrazaMember_lbl" xml:lang="en-US" id="ions_BiogenCollaborationSpinrazaMember_lbl">Collaboration agreement entered into with Biogen Inc. in January 2012 to develop and commercialize nusinersen for the treatment of spinal muscular atrophy, or SMA, a severe motor-neuron disease that is the leading genetic cause of infant mortality.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationSpinrazaMember" xlink:to="ions_BiogenCollaborationSpinrazaMember_lbl" xlink:title="label: BiogenCollaborationSpinrazaMember to ions_BiogenCollaborationSpinrazaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationSpinrazaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaborationSpinrazaMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaborationSpinrazaMember_lbl1">Biogen Collaboration, Spinraza [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationSpinrazaMember" xlink:to="ions_BiogenCollaborationSpinrazaMember_lbl1" xlink:title="label: BiogenCollaborationSpinrazaMember to ions_BiogenCollaborationSpinrazaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationSpinrazaMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaborationSpinrazaMember" xml:lang="en-US" id="ions_BiogenCollaborationSpinrazaMember">SPINRAZA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationSpinrazaMember" xlink:to="ions_BiogenCollaborationSpinrazaMember" xlink:title="label: BiogenCollaborationSpinrazaMember to ions_BiogenCollaborationSpinrazaMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:label="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:title="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" xml:lang="en-US" id="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl">Collaboration agreement entered into with Biogen Inc. in December 2017 to identify new antisense oligonucleotide drug candidates for the treatment of spinal muscular atrophy, or SMA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:to="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" xlink:title="label: BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember to ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1">Biogen Collaboration, New Antisense Medicines for Treatment of SMA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:to="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" xlink:title="label: BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember to ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xml:lang="en-US" id="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember">New Antisense Medicines for the Treatment of SMA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:to="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:title="label: BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember to ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AttrvPnMember" xlink:label="AttrvPnMember" xlink:title="AttrvPnMember" />
    <link:label xlink:type="resource" xlink:label="ions_AttrvPnMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AttrvPnMember_lbl" xml:lang="en-US" id="ions_AttrvPnMember_lbl">ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AttrvPnMember" xlink:to="ions_AttrvPnMember_lbl" xlink:title="label: AttrvPnMember to ions_AttrvPnMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AttrvPnMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AttrvPnMember_lbl1" xml:lang="en-US" id="ions_AttrvPnMember_lbl1">ATTRv-PN [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AttrvPnMember" xlink:to="ions_AttrvPnMember_lbl1" xlink:title="label: AttrvPnMember to ions_AttrvPnMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AttrvPnMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AttrvPnMember" xml:lang="en-US" id="ions_AttrvPnMember">ATTRv-PN [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AttrvPnMember" xlink:to="ions_AttrvPnMember" xlink:title="label: AttrvPnMember to ions_AttrvPnMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:label="RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:title="RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl">Royalty percentage received on sales of a medicine in the United States by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates to ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl1">Royalty percentage received on sales of medicine in United States</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates to ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates">Royalty percentage received on sales of medicine in U.S.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates to ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfMaterialComponents" xlink:label="NumberOfMaterialComponents" xlink:title="NumberOfMaterialComponents" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfMaterialComponents_lbl" xml:lang="en-US" id="ions_NumberOfMaterialComponents_lbl">The number of material components identified in the collaboration agreement under Accounting Standards Codification (ASC) 808, Collaborative Arrangements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents_lbl" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfMaterialComponents_lbl1" xml:lang="en-US" id="ions_NumberOfMaterialComponents_lbl1">Number of material components</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents_lbl1" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfMaterialComponents" xml:lang="en-US" id="ions_NumberOfMaterialComponents">Number of material components</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:label="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:title="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl">Percentage of costs associated with the ongoing global Phase 3 development program paid by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1">Percentage of costs associated with ongoing global Phase 3 development program paid by Collaboration Partner</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner">Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NovartisCollaborationsMember" xlink:label="NovartisCollaborationsMember" xlink:title="NovartisCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NovartisCollaborationsMember_lbl" xml:lang="en-US" id="ions_NovartisCollaborationsMember_lbl">Collaboration agreements entered into with Novartis International AG (Novartis).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationsMember" xlink:to="ions_NovartisCollaborationsMember_lbl" xlink:title="label: NovartisCollaborationsMember to ions_NovartisCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NovartisCollaborationsMember_lbl1" xml:lang="en-US" id="ions_NovartisCollaborationsMember_lbl1">Novartis Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationsMember" xlink:to="ions_NovartisCollaborationsMember_lbl1" xlink:title="label: NovartisCollaborationsMember to ions_NovartisCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationsMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NovartisCollaborationsMember" xml:lang="en-US" id="ions_NovartisCollaborationsMember">Novartis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationsMember" xlink:to="ions_NovartisCollaborationsMember" xlink:title="label: NovartisCollaborationsMember to ions_NovartisCollaborationsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:label="NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:title="NovartisCollaborationLpADrivenCardiovascularDiseaseMember" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl" xml:lang="en-US" id="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl">Collaboration agreement entered into with Novartis International AG (Novartis) in August 2023 for the discovery, development and commercialization of a novel medicine for patients with lipoprotein(a), or Lp(a)-driven cardiovascular disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:to="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl" xlink:title="label: NovartisCollaborationLpADrivenCardiovascularDiseaseMember to ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl1" xml:lang="en-US" id="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl1">Novartis Collaboration, Lp(a)-Driven Cardiovascular Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:to="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl1" xlink:title="label: NovartisCollaborationLpADrivenCardiovascularDiseaseMember to ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xml:lang="en-US" id="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember">Lp(a)-Driven Cardiovascular Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:to="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:title="label: NovartisCollaborationLpADrivenCardiovascularDiseaseMember to ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NovartisCollaborationPelacarsenMember" xlink:label="NovartisCollaborationPelacarsenMember" xlink:title="NovartisCollaborationPelacarsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationPelacarsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NovartisCollaborationPelacarsenMember_lbl" xml:lang="en-US" id="ions_NovartisCollaborationPelacarsenMember_lbl">Collaboration agreement entered into with Novartis International AG (Novartis) in January 2017 to develop and commercialize pelacarsen.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationPelacarsenMember" xlink:to="ions_NovartisCollaborationPelacarsenMember_lbl" xlink:title="label: NovartisCollaborationPelacarsenMember to ions_NovartisCollaborationPelacarsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationPelacarsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NovartisCollaborationPelacarsenMember_lbl1" xml:lang="en-US" id="ions_NovartisCollaborationPelacarsenMember_lbl1">Novartis Collaboration, Pelacarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationPelacarsenMember" xlink:to="ions_NovartisCollaborationPelacarsenMember_lbl1" xlink:title="label: NovartisCollaborationPelacarsenMember to ions_NovartisCollaborationPelacarsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationPelacarsenMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NovartisCollaborationPelacarsenMember" xml:lang="en-US" id="ions_NovartisCollaborationPelacarsenMember">Pelacarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationPelacarsenMember" xlink:to="ions_NovartisCollaborationPelacarsenMember" xlink:title="label: NovartisCollaborationPelacarsenMember to ions_NovartisCollaborationPelacarsenMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PelacarsenActivePharmaceuticalIngredientMember" xlink:label="PelacarsenActivePharmaceuticalIngredientMember" xlink:title="PelacarsenActivePharmaceuticalIngredientMember" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl" xml:lang="en-US" id="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl">The active pharmaceutical ingredient, or API, for Pelacarsen, an antisense therapy with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of the lipoprotein Lp(a).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenActivePharmaceuticalIngredientMember" xlink:to="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl" xlink:title="label: PelacarsenActivePharmaceuticalIngredientMember to ions_PelacarsenActivePharmaceuticalIngredientMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl1" xml:lang="en-US" id="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl1">Pelacarsen Active Pharmaceutical Ingredient [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenActivePharmaceuticalIngredientMember" xlink:to="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl1" xlink:title="label: PelacarsenActivePharmaceuticalIngredientMember to ions_PelacarsenActivePharmaceuticalIngredientMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenActivePharmaceuticalIngredientMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PelacarsenActivePharmaceuticalIngredientMember" xml:lang="en-US" id="ions_PelacarsenActivePharmaceuticalIngredientMember">Pelacarsen API [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenActivePharmaceuticalIngredientMember" xlink:to="ions_PelacarsenActivePharmaceuticalIngredientMember" xlink:title="label: PelacarsenActivePharmaceuticalIngredientMember to ions_PelacarsenActivePharmaceuticalIngredientMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PremiumReceivedOnSharesIssued" xlink:label="PremiumReceivedOnSharesIssued" xlink:title="PremiumReceivedOnSharesIssued" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumReceivedOnSharesIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PremiumReceivedOnSharesIssued_lbl" xml:lang="en-US" id="ions_PremiumReceivedOnSharesIssued_lbl">The total amount of the premium received over the trading price of common stock at the time of purchase.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumReceivedOnSharesIssued" xlink:to="ions_PremiumReceivedOnSharesIssued_lbl" xlink:title="label: PremiumReceivedOnSharesIssued to ions_PremiumReceivedOnSharesIssued_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumReceivedOnSharesIssued_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PremiumReceivedOnSharesIssued_lbl1" xml:lang="en-US" id="ions_PremiumReceivedOnSharesIssued_lbl1">Premium received on shares issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumReceivedOnSharesIssued" xlink:to="ions_PremiumReceivedOnSharesIssued_lbl1" xlink:title="label: PremiumReceivedOnSharesIssued to ions_PremiumReceivedOnSharesIssued_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumReceivedOnSharesIssued" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PremiumReceivedOnSharesIssued" xml:lang="en-US" id="ions_PremiumReceivedOnSharesIssued">Premium received on shares issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumReceivedOnSharesIssued" xlink:to="ions_PremiumReceivedOnSharesIssued" xlink:title="label: PremiumReceivedOnSharesIssued to ions_PremiumReceivedOnSharesIssued" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:label="PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:title="PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl">The potential premium received if common stock was purchased in the future under a Stock Purchase Agreement (SPA) in conjunction with the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl" xlink:title="label: PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture to ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl1" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl1">Potential premium received if common stock was purchased in future</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl1" xlink:title="label: PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture to ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture">Potential premium received if common stock was purchased in the future</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:title="label: PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture to ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PtcTherapeuticsCollaborationMember" xlink:label="PtcTherapeuticsCollaborationMember" xlink:title="PtcTherapeuticsCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_PtcTherapeuticsCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PtcTherapeuticsCollaborationMember_lbl" xml:lang="en-US" id="ions_PtcTherapeuticsCollaborationMember_lbl">Exclusive license agreement entered into with PTC Therapeutics in August 2018 to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PtcTherapeuticsCollaborationMember" xlink:to="ions_PtcTherapeuticsCollaborationMember_lbl" xlink:title="label: PtcTherapeuticsCollaborationMember to ions_PtcTherapeuticsCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PtcTherapeuticsCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PtcTherapeuticsCollaborationMember_lbl1" xml:lang="en-US" id="ions_PtcTherapeuticsCollaborationMember_lbl1">PTC Therapeutics Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PtcTherapeuticsCollaborationMember" xlink:to="ions_PtcTherapeuticsCollaborationMember_lbl1" xlink:title="label: PtcTherapeuticsCollaborationMember to ions_PtcTherapeuticsCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PtcTherapeuticsCollaborationMember" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_PtcTherapeuticsCollaborationMember" xml:lang="en-US" id="ions_PtcTherapeuticsCollaborationMember">PTC Therapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PtcTherapeuticsCollaborationMember" xlink:to="ions_PtcTherapeuticsCollaborationMember" xlink:title="label: PtcTherapeuticsCollaborationMember to ions_PtcTherapeuticsCollaborationMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl">Royalty percentage received on the net sales of each medicine from the collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner to ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl1">Royalty percentage received on net sales of each medicine from collaboration partner</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner to ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner">Royalty percentage received on net sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner to ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfTherapeuticPrograms" xlink:label="NumberOfTherapeuticPrograms" xlink:title="NumberOfTherapeuticPrograms" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticPrograms_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfTherapeuticPrograms_lbl" xml:lang="en-US" id="ions_NumberOfTherapeuticPrograms_lbl">The number of therapeutic programs with exclusive license rights under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticPrograms" xlink:to="ions_NumberOfTherapeuticPrograms_lbl" xlink:title="label: NumberOfTherapeuticPrograms to ions_NumberOfTherapeuticPrograms_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticPrograms_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfTherapeuticPrograms_lbl1" xml:lang="en-US" id="ions_NumberOfTherapeuticPrograms_lbl1">Number of therapeutic programs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticPrograms" xlink:to="ions_NumberOfTherapeuticPrograms_lbl1" xlink:title="label: NumberOfTherapeuticPrograms to ions_NumberOfTherapeuticPrograms_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:label="NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:title="NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl">The number of therapeutic targets granted by the partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xlink:title="label: NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1">Number of therapeutic targets granted by partner under collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xlink:title="label: NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement">Number of therapeutic targets granted to Ionis</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:title="label: NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:label="NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:title="NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xml:lang="en-US" id="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl">The number of unnamed therapeutic targets granted by the partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xlink:title="label: NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1">Number of unnamed therapeutic targets granted by partner under collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xlink:title="label: NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xml:lang="en-US" id="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement">Number of unnamed therapeutic targets granted to Ionis</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:title="label: NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AlnylamCollaborationMember" xlink:label="AlnylamCollaborationMember" xlink:title="AlnylamCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AlnylamCollaborationMember_lbl" xml:lang="en-US" id="ions_AlnylamCollaborationMember_lbl">Collaboration agreement entered into with Alnylam Pharmaceuticals, Inc. in March 2004 to develop and commercialize RNAi therapeutics.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember_lbl" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AlnylamCollaborationMember_lbl1" xml:lang="en-US" id="ions_AlnylamCollaborationMember_lbl1">Alnylam Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember_lbl1" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AlnylamCollaborationMember" xml:lang="en-US" id="ions_AlnylamCollaborationMember">Alnylam [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:label="NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:title="NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl">The number of therapeutic targets granted to the partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl" xlink:title="label: NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl1">Number of therapeutic targets granted to partner under collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl1" xlink:title="label: NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement">Number of therapeutic targets granted by Ionis</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:title="label: NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PaymentsMadeUnderCollaborationAgreement" xlink:label="PaymentsMadeUnderCollaborationAgreement" xlink:title="PaymentsMadeUnderCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsMadeUnderCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentsMadeUnderCollaborationAgreement_lbl" xml:lang="en-US" id="ions_PaymentsMadeUnderCollaborationAgreement_lbl">Represents the cash outflow for payments made under the collaboration agreement for the reimbursement of support received in connection with the Company's Huntington's disease program.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsMadeUnderCollaborationAgreement" xlink:to="ions_PaymentsMadeUnderCollaborationAgreement_lbl" xlink:title="label: PaymentsMadeUnderCollaborationAgreement to ions_PaymentsMadeUnderCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsMadeUnderCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentsMadeUnderCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_PaymentsMadeUnderCollaborationAgreement_lbl1">Payments made under collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsMadeUnderCollaborationAgreement" xlink:to="ions_PaymentsMadeUnderCollaborationAgreement_lbl1" xlink:title="label: PaymentsMadeUnderCollaborationAgreement to ions_PaymentsMadeUnderCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsMadeUnderCollaborationAgreement" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PaymentsMadeUnderCollaborationAgreement" xml:lang="en-US" id="ions_PaymentsMadeUnderCollaborationAgreement">Payment of license fee</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsMadeUnderCollaborationAgreement" xlink:to="ions_PaymentsMadeUnderCollaborationAgreement" xlink:title="label: PaymentsMadeUnderCollaborationAgreement to ions_PaymentsMadeUnderCollaborationAgreement" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_InvestmentInEquitySecuritiesFvNi" xlink:label="InvestmentInEquitySecuritiesFvNi" xlink:title="InvestmentInEquitySecuritiesFvNi" />
    <link:label xlink:type="resource" xlink:label="ions_InvestmentInEquitySecuritiesFvNi_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_InvestmentInEquitySecuritiesFvNi_lbl" xml:lang="en-US" id="ions_InvestmentInEquitySecuritiesFvNi_lbl">Acquisition of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentInEquitySecuritiesFvNi" xlink:to="ions_InvestmentInEquitySecuritiesFvNi_lbl" xlink:title="label: InvestmentInEquitySecuritiesFvNi to ions_InvestmentInEquitySecuritiesFvNi_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_InvestmentInEquitySecuritiesFvNi_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_InvestmentInEquitySecuritiesFvNi_lbl1" xml:lang="en-US" id="ions_InvestmentInEquitySecuritiesFvNi_lbl1">Investment in Equity Securities, FV-NI</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentInEquitySecuritiesFvNi" xlink:to="ions_InvestmentInEquitySecuritiesFvNi_lbl1" xlink:title="label: InvestmentInEquitySecuritiesFvNi to ions_InvestmentInEquitySecuritiesFvNi_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_InvestmentInEquitySecuritiesFvNi" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_InvestmentInEquitySecuritiesFvNi" xml:lang="en-US" id="ions_InvestmentInEquitySecuritiesFvNi">Equity investment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentInEquitySecuritiesFvNi" xlink:to="ions_InvestmentInEquitySecuritiesFvNi" xlink:title="label: InvestmentInEquitySecuritiesFvNi to ions_InvestmentInEquitySecuritiesFvNi" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LockUpAgreementTermOfTradingRestriction" xlink:label="LockUpAgreementTermOfTradingRestriction" xlink:title="LockUpAgreementTermOfTradingRestriction" />
    <link:label xlink:type="resource" xlink:label="ions_LockUpAgreementTermOfTradingRestriction_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LockUpAgreementTermOfTradingRestriction_lbl" xml:lang="en-US" id="ions_LockUpAgreementTermOfTradingRestriction_lbl">Period after completion of initial public offering by an equity investee and restriction to sell equity holding in the investee, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LockUpAgreementTermOfTradingRestriction" xlink:to="ions_LockUpAgreementTermOfTradingRestriction_lbl" xlink:title="label: LockUpAgreementTermOfTradingRestriction to ions_LockUpAgreementTermOfTradingRestriction_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LockUpAgreementTermOfTradingRestriction_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LockUpAgreementTermOfTradingRestriction_lbl1" xml:lang="en-US" id="ions_LockUpAgreementTermOfTradingRestriction_lbl1">Lock up Agreement, Term of Trading Restriction</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LockUpAgreementTermOfTradingRestriction" xlink:to="ions_LockUpAgreementTermOfTradingRestriction_lbl1" xlink:title="label: LockUpAgreementTermOfTradingRestriction to ions_LockUpAgreementTermOfTradingRestriction_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LockUpAgreementTermOfTradingRestriction" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LockUpAgreementTermOfTradingRestriction" xml:lang="en-US" id="ions_LockUpAgreementTermOfTradingRestriction">Trading restriction period under lock up agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LockUpAgreementTermOfTradingRestriction" xlink:to="ions_LockUpAgreementTermOfTradingRestriction" xlink:title="label: LockUpAgreementTermOfTradingRestriction to ions_LockUpAgreementTermOfTradingRestriction" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_BicycleCollaborationMember" xlink:label="BicycleCollaborationMember" xlink:title="BicycleCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_BicycleCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BicycleCollaborationMember_lbl" xml:lang="en-US" id="ions_BicycleCollaborationMember_lbl">Collaboration agreement entered into with Bicycle Therapeutics in December 2020, including an option to license Bicycle's peptide technology to potentially increase the delivery capabilities of the Company's Ligand Conjugated Antisense, or LICA, medicines.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BicycleCollaborationMember" xlink:to="ions_BicycleCollaborationMember_lbl" xlink:title="label: BicycleCollaborationMember to ions_BicycleCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BicycleCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BicycleCollaborationMember_lbl1" xml:lang="en-US" id="ions_BicycleCollaborationMember_lbl1">Bicycle Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BicycleCollaborationMember" xlink:to="ions_BicycleCollaborationMember_lbl1" xlink:title="label: BicycleCollaborationMember to ions_BicycleCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BicycleCollaborationMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BicycleCollaborationMember" xml:lang="en-US" id="ions_BicycleCollaborationMember">Bicycle License Agreement [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BicycleCollaborationMember" xlink:to="ions_BicycleCollaborationMember" xlink:title="label: BicycleCollaborationMember to ions_BicycleCollaborationMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AccruedCommercialExpensesCurrent" xlink:label="AccruedCommercialExpensesCurrent" xlink:title="AccruedCommercialExpensesCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedCommercialExpensesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedCommercialExpensesCurrent_lbl" xml:lang="en-US" id="ions_AccruedCommercialExpensesCurrent_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for commercial expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedCommercialExpensesCurrent" xlink:to="ions_AccruedCommercialExpensesCurrent_lbl" xlink:title="label: AccruedCommercialExpensesCurrent to ions_AccruedCommercialExpensesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedCommercialExpensesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedCommercialExpensesCurrent_lbl1" xml:lang="en-US" id="ions_AccruedCommercialExpensesCurrent_lbl1">Accrued commercial expenses, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedCommercialExpensesCurrent" xlink:to="ions_AccruedCommercialExpensesCurrent_lbl1" xlink:title="label: AccruedCommercialExpensesCurrent to ions_AccruedCommercialExpensesCurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedCommercialExpensesCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedCommercialExpensesCurrent" xml:lang="en-US" id="ions_AccruedCommercialExpensesCurrent">Commercial expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedCommercialExpensesCurrent" xlink:to="ions_AccruedCommercialExpensesCurrent" xlink:title="label: AccruedCommercialExpensesCurrent to ions_AccruedCommercialExpensesCurrent" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AccruedClinicalDevelopmentExpenses" xlink:label="AccruedClinicalDevelopmentExpenses" xlink:title="AccruedClinicalDevelopmentExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalDevelopmentExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedClinicalDevelopmentExpenses_lbl" xml:lang="en-US" id="ions_AccruedClinicalDevelopmentExpenses_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for clinical development expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalDevelopmentExpenses" xlink:to="ions_AccruedClinicalDevelopmentExpenses_lbl" xlink:title="label: AccruedClinicalDevelopmentExpenses to ions_AccruedClinicalDevelopmentExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalDevelopmentExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedClinicalDevelopmentExpenses_lbl1" xml:lang="en-US" id="ions_AccruedClinicalDevelopmentExpenses_lbl1">Accrued clinical development expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalDevelopmentExpenses" xlink:to="ions_AccruedClinicalDevelopmentExpenses_lbl1" xlink:title="label: AccruedClinicalDevelopmentExpenses to ions_AccruedClinicalDevelopmentExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalDevelopmentExpenses" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_AccruedClinicalDevelopmentExpenses" xml:lang="en-US" id="ions_AccruedClinicalDevelopmentExpenses">Clinical expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalDevelopmentExpenses" xlink:to="ions_AccruedClinicalDevelopmentExpenses" xlink:title="label: AccruedClinicalDevelopmentExpenses to ions_AccruedClinicalDevelopmentExpenses" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_AccruedInLicensingFeesCurrent" xlink:label="AccruedInLicensingFeesCurrent" xlink:title="AccruedInLicensingFeesCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedInLicensingFeesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedInLicensingFeesCurrent_lbl" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for in-licensing fees under collaboration agreements. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent_lbl" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedInLicensingFeesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedInLicensingFeesCurrent_lbl1" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent_lbl1">Accrued in-licensing fees, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent_lbl1" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedInLicensingFeesCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedInLicensingFeesCurrent" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent">In-licensing expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_PropertyPlantAndEquipmentExcludingLandMember" xlink:label="PropertyPlantAndEquipmentExcludingLandMember" xlink:title="PropertyPlantAndEquipmentExcludingLandMember" />
    <link:label xlink:type="resource" xlink:label="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" xml:lang="en-US" id="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl">Physical assets used in the normal conduct of business and not intended for resale, excluding land. Examples include, but are not limited to, buildings, land and leasehold improvements, machinery and equipment, office equipment, and furniture and fixtures.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentExcludingLandMember" xlink:to="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" xlink:title="label: PropertyPlantAndEquipmentExcludingLandMember to ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" xml:lang="en-US" id="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1">Property, Plant and Equipment, Excluding Land [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentExcludingLandMember" xlink:to="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" xlink:title="label: PropertyPlantAndEquipmentExcludingLandMember to ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_BiogenCollaboration2013StrategicNeurologyMember" xlink:label="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="BiogenCollaboration2013StrategicNeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl">Collaborative agreement entered into with Biogen Inc. in September 2013 focused on applying antisense technology to advance the treatment of neurodegenerative diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1">Biogen Collaboration, 2013 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember">2013 Strategic Neurology Collaboration with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_OtherMember" xlink:label="OtherMember" xlink:title="OtherMember" />
    <link:label xlink:type="resource" xlink:label="ions_OtherMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtherMember_lbl" xml:lang="en-US" id="ions_OtherMember_lbl">Revenue from the sale of other medicines commercially.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherMember" xlink:to="ions_OtherMember_lbl" xlink:title="label: OtherMember to ions_OtherMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtherMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtherMember_lbl1" xml:lang="en-US" id="ions_OtherMember_lbl1">Other [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherMember" xlink:to="ions_OtherMember_lbl1" xlink:title="label: OtherMember to ions_OtherMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OtherMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OtherMember" xml:lang="en-US" id="ions_OtherMember">Other Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherMember" xlink:to="ions_OtherMember" xlink:title="label: OtherMember to ions_OtherMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_OtsukaCollaborationDonidalorsenMember" xlink:label="OtsukaCollaborationDonidalorsenMember" xlink:title="OtsukaCollaborationDonidalorsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaCollaborationDonidalorsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtsukaCollaborationDonidalorsenMember_lbl" xml:lang="en-US" id="ions_OtsukaCollaborationDonidalorsenMember_lbl">Collaboration agreement entered into with Otsuka Pharmaceutical Co., Ltd. (Otsuka) in December 2023 to develop and commercialize donidalorsen, an investigational ligand-conjugated antisense (LICA) medicine designed to target the prekallikrein (PKK) pathway.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaCollaborationDonidalorsenMember" xlink:to="ions_OtsukaCollaborationDonidalorsenMember_lbl" xlink:title="label: OtsukaCollaborationDonidalorsenMember to ions_OtsukaCollaborationDonidalorsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaCollaborationDonidalorsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtsukaCollaborationDonidalorsenMember_lbl1" xml:lang="en-US" id="ions_OtsukaCollaborationDonidalorsenMember_lbl1">Otsuka Collaboration, Donidalorsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaCollaborationDonidalorsenMember" xlink:to="ions_OtsukaCollaborationDonidalorsenMember_lbl1" xlink:title="label: OtsukaCollaborationDonidalorsenMember to ions_OtsukaCollaborationDonidalorsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaCollaborationDonidalorsenMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OtsukaCollaborationDonidalorsenMember" xml:lang="en-US" id="ions_OtsukaCollaborationDonidalorsenMember">Donidalorsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaCollaborationDonidalorsenMember" xlink:to="ions_OtsukaCollaborationDonidalorsenMember" xlink:title="label: OtsukaCollaborationDonidalorsenMember to ions_OtsukaCollaborationDonidalorsenMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ResearchAndDevelopmentServicesForDonidalorsenMember" xlink:label="ResearchAndDevelopmentServicesForDonidalorsenMember" xlink:title="ResearchAndDevelopmentServicesForDonidalorsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForDonidalorsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForDonidalorsenMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForDonidalorsenMember_lbl">Research and development (R&amp;D) services for donidalorsen, an investigational ligand-conjugated antisense (LICA) medicine designed to target the prekallikrein (PKK) pathway.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForDonidalorsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForDonidalorsenMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesForDonidalorsenMember to ions_ResearchAndDevelopmentServicesForDonidalorsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForDonidalorsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForDonidalorsenMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForDonidalorsenMember_lbl1">Research and Development Services for Donidalorsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForDonidalorsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForDonidalorsenMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesForDonidalorsenMember to ions_ResearchAndDevelopmentServicesForDonidalorsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForDonidalorsenMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForDonidalorsenMember" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForDonidalorsenMember">R&amp;D Services for Donidalorsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForDonidalorsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForDonidalorsenMember" xlink:title="label: ResearchAndDevelopmentServicesForDonidalorsenMember to ions_ResearchAndDevelopmentServicesForDonidalorsenMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_LicenseOfDonidalorsenMember" xlink:label="LicenseOfDonidalorsenMember" xlink:title="LicenseOfDonidalorsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_LicenseOfDonidalorsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LicenseOfDonidalorsenMember_lbl" xml:lang="en-US" id="ions_LicenseOfDonidalorsenMember_lbl">License of donidalorsen, an investigational ligand-conjugated antisense (LICA) medicine designed to target the prekallikrein (PKK) pathway.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicenseOfDonidalorsenMember" xlink:to="ions_LicenseOfDonidalorsenMember_lbl" xlink:title="label: LicenseOfDonidalorsenMember to ions_LicenseOfDonidalorsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LicenseOfDonidalorsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LicenseOfDonidalorsenMember_lbl1" xml:lang="en-US" id="ions_LicenseOfDonidalorsenMember_lbl1">License of Donidalorsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicenseOfDonidalorsenMember" xlink:to="ions_LicenseOfDonidalorsenMember_lbl1" xlink:title="label: LicenseOfDonidalorsenMember to ions_LicenseOfDonidalorsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LicenseOfDonidalorsenMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LicenseOfDonidalorsenMember" xml:lang="en-US" id="ions_LicenseOfDonidalorsenMember">License of Donidalorsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicenseOfDonidalorsenMember" xlink:to="ions_LicenseOfDonidalorsenMember" xlink:title="label: LicenseOfDonidalorsenMember to ions_LicenseOfDonidalorsenMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_IonisOperationsMember" xlink:label="IonisOperationsMember" xlink:title="IonisOperationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_IonisOperationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisOperationsMember_lbl" xml:lang="en-US" id="ions_IonisOperationsMember_lbl">Operations focused on the research, development and commercialization of RNA-targeted medicines to bring better futures to people with serious diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisOperationsMember" xlink:to="ions_IonisOperationsMember_lbl" xlink:title="label: IonisOperationsMember to ions_IonisOperationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IonisOperationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IonisOperationsMember_lbl1" xml:lang="en-US" id="ions_IonisOperationsMember_lbl1">Ionis Operations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisOperationsMember" xlink:to="ions_IonisOperationsMember_lbl1" xlink:title="label: IonisOperationsMember to ions_IonisOperationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IonisOperationsMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IonisOperationsMember" xml:lang="en-US" id="ions_IonisOperationsMember">Ionis Operations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisOperationsMember" xlink:to="ions_IonisOperationsMember" xlink:title="label: IonisOperationsMember to ions_IonisOperationsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DrugDiscoveryExpenses" xlink:label="DrugDiscoveryExpenses" xlink:title="DrugDiscoveryExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_DrugDiscoveryExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DrugDiscoveryExpenses_lbl" xml:lang="en-US" id="ions_DrugDiscoveryExpenses_lbl">Expenses related to drug discovery research and advancing the Company's core technology.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DrugDiscoveryExpenses" xlink:to="ions_DrugDiscoveryExpenses_lbl" xlink:title="label: DrugDiscoveryExpenses to ions_DrugDiscoveryExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DrugDiscoveryExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DrugDiscoveryExpenses_lbl1" xml:lang="en-US" id="ions_DrugDiscoveryExpenses_lbl1">Drug Discovery Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DrugDiscoveryExpenses" xlink:to="ions_DrugDiscoveryExpenses_lbl1" xlink:title="label: DrugDiscoveryExpenses to ions_DrugDiscoveryExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DrugDiscoveryExpenses" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DrugDiscoveryExpenses" xml:lang="en-US" id="ions_DrugDiscoveryExpenses">Drug discovery</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DrugDiscoveryExpenses" xlink:to="ions_DrugDiscoveryExpenses" xlink:title="label: DrugDiscoveryExpenses to ions_DrugDiscoveryExpenses" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_DrugDevelopmentExpenses" xlink:label="DrugDevelopmentExpenses" xlink:title="DrugDevelopmentExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_DrugDevelopmentExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DrugDevelopmentExpenses_lbl" xml:lang="en-US" id="ions_DrugDevelopmentExpenses_lbl">Expenses related to drug development, including expenses for marketed medicines and those in Phase 3 development.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DrugDevelopmentExpenses" xlink:to="ions_DrugDevelopmentExpenses_lbl" xlink:title="label: DrugDevelopmentExpenses to ions_DrugDevelopmentExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DrugDevelopmentExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DrugDevelopmentExpenses_lbl1" xml:lang="en-US" id="ions_DrugDevelopmentExpenses_lbl1">Drug Development Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DrugDevelopmentExpenses" xlink:to="ions_DrugDevelopmentExpenses_lbl1" xlink:title="label: DrugDevelopmentExpenses to ions_DrugDevelopmentExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DrugDevelopmentExpenses" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DrugDevelopmentExpenses" xml:lang="en-US" id="ions_DrugDevelopmentExpenses">Drug development</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DrugDevelopmentExpenses" xlink:to="ions_DrugDevelopmentExpenses" xlink:title="label: DrugDevelopmentExpenses to ions_DrugDevelopmentExpenses" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_MedicalAffairsExpenses" xlink:label="MedicalAffairsExpenses" xlink:title="MedicalAffairsExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_MedicalAffairsExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MedicalAffairsExpenses_lbl" xml:lang="en-US" id="ions_MedicalAffairsExpenses_lbl">Expenses related to medical affairs for funding and coordinating investigator-sponsored trials, communicating scientific and clinical information to healthcare providers, medical professionals and patients, and managing publications.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicalAffairsExpenses" xlink:to="ions_MedicalAffairsExpenses_lbl" xlink:title="label: MedicalAffairsExpenses to ions_MedicalAffairsExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MedicalAffairsExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MedicalAffairsExpenses_lbl1" xml:lang="en-US" id="ions_MedicalAffairsExpenses_lbl1">Medical Affairs Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicalAffairsExpenses" xlink:to="ions_MedicalAffairsExpenses_lbl1" xlink:title="label: MedicalAffairsExpenses to ions_MedicalAffairsExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MedicalAffairsExpenses" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MedicalAffairsExpenses" xml:lang="en-US" id="ions_MedicalAffairsExpenses">Medical affairs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicalAffairsExpenses" xlink:to="ions_MedicalAffairsExpenses" xlink:title="label: MedicalAffairsExpenses to ions_MedicalAffairsExpenses" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ManufacturingAndDevelopmentChemistryExpenses" xlink:label="ManufacturingAndDevelopmentChemistryExpenses" xlink:title="ManufacturingAndDevelopmentChemistryExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_ManufacturingAndDevelopmentChemistryExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ManufacturingAndDevelopmentChemistryExpenses_lbl" xml:lang="en-US" id="ions_ManufacturingAndDevelopmentChemistryExpenses_lbl">Expenses related to manufacturing and development chemistry for providing drug supplies to drug development and our collaboration partners, including personnel costs, specialized chemicals for oligonucleotide manufacturing, validation batches to support regulatory approvals, laboratory supplies and outside services.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingAndDevelopmentChemistryExpenses" xlink:to="ions_ManufacturingAndDevelopmentChemistryExpenses_lbl" xlink:title="label: ManufacturingAndDevelopmentChemistryExpenses to ions_ManufacturingAndDevelopmentChemistryExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ManufacturingAndDevelopmentChemistryExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ManufacturingAndDevelopmentChemistryExpenses_lbl1" xml:lang="en-US" id="ions_ManufacturingAndDevelopmentChemistryExpenses_lbl1">Manufacturing and Development Chemistry Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingAndDevelopmentChemistryExpenses" xlink:to="ions_ManufacturingAndDevelopmentChemistryExpenses_lbl1" xlink:title="label: ManufacturingAndDevelopmentChemistryExpenses to ions_ManufacturingAndDevelopmentChemistryExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ManufacturingAndDevelopmentChemistryExpenses" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ManufacturingAndDevelopmentChemistryExpenses" xml:lang="en-US" id="ions_ManufacturingAndDevelopmentChemistryExpenses">Manufacturing and development chemistry</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingAndDevelopmentChemistryExpenses" xlink:to="ions_ManufacturingAndDevelopmentChemistryExpenses" xlink:title="label: ManufacturingAndDevelopmentChemistryExpenses to ions_ManufacturingAndDevelopmentChemistryExpenses" />
    <link:loc xlink:type="locator" xlink:href="ions-20241231.xsd#ions_ResearchAndDevelopmentSupportExpenses" xlink:label="ResearchAndDevelopmentSupportExpenses" xlink:title="ResearchAndDevelopmentSupportExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentSupportExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentSupportExpenses_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentSupportExpenses_lbl">Expenses related to research and development support such as rent, repair and maintenance for buildings and equipment, utilities, depreciation of laboratory equipment and facilities, amortization of intellectual property, information technology costs, procurement costs and waste disposal costs.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentSupportExpenses" xlink:to="ions_ResearchAndDevelopmentSupportExpenses_lbl" xlink:title="label: ResearchAndDevelopmentSupportExpenses to ions_ResearchAndDevelopmentSupportExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentSupportExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentSupportExpenses_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentSupportExpenses_lbl1">Research and Development Support Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentSupportExpenses" xlink:to="ions_ResearchAndDevelopmentSupportExpenses_lbl1" xlink:title="label: ResearchAndDevelopmentSupportExpenses to ions_ResearchAndDevelopmentSupportExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentSupportExpenses" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentSupportExpenses" xml:lang="en-US" id="ions_ResearchAndDevelopmentSupportExpenses">R&amp;D support</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentSupportExpenses" xlink:to="ions_ResearchAndDevelopmentSupportExpenses" xlink:title="label: ResearchAndDevelopmentSupportExpenses to ions_ResearchAndDevelopmentSupportExpenses" />
  </link:labelLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.PRE
<SEQUENCE>12
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<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929279504">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Document and Entity Information - USD ($)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
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<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Feb. 13, 2025</div></th>
<th class="th"><div>Jun. 30, 2024</div></th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_CoverAbstract', window );"><strong>Cover [Abstract]</strong></a></td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentType', window );">Document Type</a></td>
<td class="text">10-K<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_AmendmentFlag', window );">Amendment Flag</a></td>
<td class="text">false<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentAnnualReport', window );">Document Annual Report</a></td>
<td class="text">true<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentPeriodEndDate', window );">Document Period End Date</a></td>
<td class="text">Dec. 31,  2024<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">--12-31<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentFiscalYearFocus', window );">Document Fiscal Year Focus</a></td>
<td class="text">2024<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentFiscalPeriodFocus', window );">Document Fiscal Period Focus</a></td>
<td class="text">FY<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentTransitionReport', window );">Document Transition Report</a></td>
<td class="text">false<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityFileNumber', window );">Entity File Number</a></td>
<td class="text">000-19125<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityRegistrantName', window );">Entity Registrant Name</a></td>
<td class="text">Ionis Pharmaceuticals, Inc<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityCentralIndexKey', window );">Entity Central Index Key</a></td>
<td class="text">0000874015<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityIncorporationStateCountryCode', window );">Entity Incorporation, State or Country Code</a></td>
<td class="text">DE<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityTaxIdentificationNumber', window );">Entity Tax Identification Number</a></td>
<td class="text">33-0336973<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressAddressLine1', window );">Entity Address, Address Line One</a></td>
<td class="text">2855 Gazelle Court<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressCityOrTown', window );">Entity Address, City or Town</a></td>
<td class="text">Carlsbad<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressStateOrProvince', window );">Entity Address, State or Province</a></td>
<td class="text">CA<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressPostalZipCode', window );">Entity Address, Postal Zip Code</a></td>
<td class="text">92010<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_CityAreaCode', window );">City Area Code</a></td>
<td class="text">760<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_LocalPhoneNumber', window );">Local Phone Number</a></td>
<td class="text">931-9200<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_Security12bTitle', window );">Title of 12(b) Security</a></td>
<td class="text">Common Stock, $.001 Par Value<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_TradingSymbol', window );">Trading Symbol</a></td>
<td class="text">IONS<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_SecurityExchangeName', window );">Security Exchange Name</a></td>
<td class="text">NASDAQ<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityWellKnownSeasonedIssuer', window );">Entity Well-known Seasoned Issuer</a></td>
<td class="text">Yes<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityVoluntaryFilers', window );">Entity Voluntary Filers</a></td>
<td class="text">No<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityCurrentReportingStatus', window );">Entity Current Reporting Status</a></td>
<td class="text">Yes<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityInteractiveDataCurrent', window );">Entity Interactive Data Current</a></td>
<td class="text">Yes<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityFilerCategory', window );">Entity Filer Category</a></td>
<td class="text">Large Accelerated Filer<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntitySmallBusiness', window );">Entity Small Business</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityEmergingGrowthCompany', window );">Entity Emerging Growth Company</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_IcfrAuditorAttestationFlag', window );">ICFR Auditor Attestation Flag</a></td>
<td class="text">true<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentFinStmtErrorCorrectionFlag', window );">Document Financial Statement Error Correction [Flag]</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityShellCompany', window );">Entity Shell Company</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityPublicFloat', window );">Entity Public Float</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 5,738,934,243<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityCommonStockSharesOutstanding', window );">Entity Common Stock, Shares Outstanding</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">158,964,772<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_AuditorFirmId', window );">Auditor Firm ID</a></td>
<td class="text">42<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_AuditorName', window );">Auditor Name</a></td>
<td class="text">Ernst & Young LLP<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_AuditorLocation', window );">Auditor Location</a></td>
<td class="text">San Diego, California<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AmendmentFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the XBRL content amends previously-filed or accepted submission.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AmendmentFlag</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AuditorFirmId">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>PCAOB issued Audit Firm Identifier</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Number 249<br> -Section 220<br> -Subsection f<br><br>Reference 3: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 40-F<br> -Number 249<br> -Section 240<br> -Subsection f<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AuditorFirmId</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:nonemptySequenceNumberItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AuditorLocation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Number 249<br> -Section 220<br> -Subsection f<br><br>Reference 3: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 40-F<br> -Number 249<br> -Section 240<br> -Subsection f<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AuditorLocation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:internationalNameItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AuditorName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Number 249<br> -Section 220<br> -Subsection f<br><br>Reference 3: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 40-F<br> -Number 249<br> -Section 240<br> -Subsection f<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AuditorName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:internationalNameItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CityAreaCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Area code of city</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CityAreaCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CoverAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cover page.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CoverAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CurrentFiscalYearEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>End date of current fiscal year in the format --MM-DD.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CurrentFiscalYearEndDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:gMonthDayItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentAnnualReport">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true only for a form used as an annual report.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Number 249<br> -Section 220<br> -Subsection f<br><br>Reference 3: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 40-F<br> -Number 249<br> -Section 240<br> -Subsection f<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentAnnualReport</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentFinStmtErrorCorrectionFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicates whether any of the financial statement period in the filing include a restatement due to error correction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 402<br> -Subsection w<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 3: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Number 249<br> -Section 220<br> -Subsection f<br><br>Reference 4: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 40-F<br> -Number 249<br> -Section 240<br> -Subsection f<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentFinStmtErrorCorrectionFlag</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentFiscalPeriodFocus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fiscal period values are FY, Q1, Q2, and Q3. 1st, 2nd and 3rd quarter 10-Q or 10-QT statements have value Q1, Q2, and Q3 respectively, with 10-K, 10-KT or other fiscal year statements having FY.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentFiscalPeriodFocus</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:fiscalPeriodItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentFiscalYearFocus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>This is focus fiscal year of the document report in YYYY format. For a 2006 annual report, which may also provide financial information from prior periods, fiscal 2006 should be given as the fiscal year focus. Example: 2006.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentFiscalYearFocus</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:gYearItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentPeriodEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For the EDGAR submission types of Form 8-K: the date of the report, the date of the earliest event reported; for the EDGAR submission types of Form N-1A: the filing date; for all other submission types: the end of the reporting or transition period. The format of the date is YYYY-MM-DD.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentPeriodEndDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:dateItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentTransitionReport">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true only for a form used as a transition report.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Forms 10-K, 10-Q, 20-F<br> -Number 240<br> -Section 13<br> -Subsection a-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentTransitionReport</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentType">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The type of document being provided (such as 10-K, 10-Q, 485BPOS, etc). The document type is limited to the same value as the supporting SEC submission type, or the word 'Other'.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentType</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:submissionTypeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressAddressLine1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Address Line 1 such as Attn, Building Name, Street Name</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressAddressLine1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressCityOrTown">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the City or Town</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressCityOrTown</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressPostalZipCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Code for the postal or zip code</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressPostalZipCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressStateOrProvince">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the state or province.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressStateOrProvince</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:stateOrProvinceItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCentralIndexKey">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A unique 10-digit SEC-issued value to identify entities that have filed disclosures with the SEC. It is commonly abbreviated as CIK.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCentralIndexKey</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:centralIndexKeyItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate number of shares or other units outstanding of each of registrant's classes of capital or common stock or other ownership interests, if and as stated on cover of related periodic report. Where multiple classes or units exist define each class/interest by adding class of stock items such as Common Class A [Member], Common Class B [Member] or Partnership Interest [Member] onto the Instrument [Domain] of the Entity Listings, Instrument.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCommonStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCurrentReportingStatus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate 'Yes' or 'No' whether registrants (1) have filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that registrants were required to file such reports), and (2) have been subject to such filing requirements for the past 90 days. This information should be based on the registrant's current or most recent filing containing the related disclosure.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCurrentReportingStatus</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityEmergingGrowthCompany">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate if registrant meets the emerging growth company criteria.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityEmergingGrowthCompany</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityFileNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Commission file number. The field allows up to 17 characters. The prefix may contain 1-3 digits, the sequence number may contain 1-8 digits, the optional suffix may contain 1-4 characters, and the fields are separated with a hyphen.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityFileNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:fileNumberItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityFilerCategory">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate whether the registrant is one of the following: Large Accelerated Filer, Accelerated Filer, Non-accelerated Filer. Definitions of these categories are stated in Rule 12b-2 of the Exchange Act. This information should be based on the registrant's current or most recent filing containing the related disclosure.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityFilerCategory</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:filerCategoryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityIncorporationStateCountryCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Two-character EDGAR code representing the state or country of incorporation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityIncorporationStateCountryCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarStateCountryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityInteractiveDataCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-T<br> -Number 232<br> -Section 405<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityInteractiveDataCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityPublicFloat">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate market value of the voting and non-voting common equity held by non-affiliates computed by reference to the price at which the common equity was last sold, or the average bid and asked price of such common equity, as of the last business day of the registrant's most recently completed second fiscal quarter.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityPublicFloat</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityRegistrantName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The exact name of the entity filing the report as specified in its charter, which is required by forms filed with the SEC.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityRegistrantName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityShellCompany">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the registrant is a shell company as defined in Rule 12b-2 of the Exchange Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityShellCompany</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntitySmallBusiness">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicates that the company is a Smaller Reporting Company (SRC).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntitySmallBusiness</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityTaxIdentificationNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The Tax Identification Number (TIN), also known as an Employer Identification Number (EIN), is a unique 9-digit value assigned by the IRS.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityTaxIdentificationNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:employerIdItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityVoluntaryFilers">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate 'Yes' or 'No' if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityVoluntaryFilers</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityWellKnownSeasonedIssuer">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate 'Yes' or 'No' if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Is used on Form Type: 10-K, 10-Q, 8-K, 20-F, 6-K, 10-K/A, 10-Q/A, 20-F/A, 6-K/A, N-CSR, N-Q, N-1A.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Securities Act<br> -Number 230<br> -Section 405<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityWellKnownSeasonedIssuer</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_IcfrAuditorAttestationFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Number 249<br> -Section 220<br> -Subsection f<br><br>Reference 3: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 40-F<br> -Number 249<br> -Section 240<br> -Subsection f<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_IcfrAuditorAttestationFlag</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_LocalPhoneNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Local phone number for entity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_LocalPhoneNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_Security12bTitle">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Title of a 12(b) registered security.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_Security12bTitle</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:securityTitleItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_SecurityExchangeName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the Exchange on which a security is registered.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection d1-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_SecurityExchangeName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarExchangeCodeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_TradingSymbol">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Trading symbol of an instrument as listed on an exchange.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_TradingSymbol</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:tradingSymbolItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931310688">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONSOLIDATED BALANCE SHEETS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsCurrentAbstract', window );"><strong>Current assets:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents</a></td>
<td class="nump">$ 242,077<span></span>
</td>
<td class="nump">$ 399,266<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShortTermInvestments', window );">Short-term investments</a></td>
<td class="nump">2,055,579<span></span>
</td>
<td class="nump">1,931,935<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrent', window );">Contracts receivable</a></td>
<td class="nump">92,188<span></span>
</td>
<td class="nump">97,778<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryNet', window );">Inventories</a></td>
<td class="nump">12,512<span></span>
</td>
<td class="nump">7,441<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherAssetsCurrent', window );">Other current assets</a></td>
<td class="nump">217,934<span></span>
</td>
<td class="nump">205,433<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsCurrent', window );">Total current assets</a></td>
<td class="nump">2,620,290<span></span>
</td>
<td class="nump">2,641,853<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="nump">94,251<span></span>
</td>
<td class="nump">71,043<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAsset', window );">Right-of-use assets</a></td>
<td class="nump">161,856<span></span>
</td>
<td class="nump">171,896<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherAssetsNoncurrent', window );">Deposits and other assets</a></td>
<td class="nump">127,278<span></span>
</td>
<td class="nump">105,280<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets</a></td>
<td class="nump">3,003,675<span></span>
</td>
<td class="nump">2,990,072<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrentAbstract', window );"><strong>Current liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccountsPayableCurrent', window );">Accounts payable</a></td>
<td class="nump">42,964<span></span>
</td>
<td class="nump">26,027<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeRelatedLiabilitiesCurrent', window );">Accrued compensation</a></td>
<td class="nump">69,614<span></span>
</td>
<td class="nump">67,727<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrent', window );">Accrued liabilities</a></td>
<td class="nump">108,438<span></span>
</td>
<td class="nump">147,894<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedIncomeTaxesCurrent', window );">Income taxes payable</a></td>
<td class="nump">34<span></span>
</td>
<td class="nump">2,151<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtCurrent', window );">0.125 percent convertible senior notes, net</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">44,332<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred contract revenue</a></td>
<td class="nump">78,989<span></span>
</td>
<td class="nump">151,128<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherLiabilitiesCurrent', window );">Other current liabilities</a></td>
<td class="nump">9,279<span></span>
</td>
<td class="nump">8,831<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrent', window );">Total current liabilities</a></td>
<td class="nump">309,318<span></span>
</td>
<td class="nump">448,090<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityNoncurrent', window );">Long-term deferred contract revenue</a></td>
<td class="nump">156,504<span></span>
</td>
<td class="nump">241,184<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Liability related to sale of future royalties, net</a></td>
<td class="nump">542,212<span></span>
</td>
<td class="nump">513,736<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityNoncurrent', window );">Long-term lease liabilities</a></td>
<td class="nump">161,805<span></span>
</td>
<td class="nump">170,875<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermLoansFromBank', window );">Long-term obligations</a></td>
<td class="nump">51,924<span></span>
</td>
<td class="nump">41,836<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Liabilities', window );">Total liabilities</a></td>
<td class="nump">2,415,324<span></span>
</td>
<td class="nump">2,603,386<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityAbstract', window );"><strong>Stockholders' equity:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockValue', window );">Common stock, $0.001 par value; 300,000,000 shares authorized, 157,908,815 and 144,340,526 shares issued and outstanding at December 31, 2024 and December 31, 2023, respectively</a></td>
<td class="nump">158<span></span>
</td>
<td class="nump">144<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdditionalPaidInCapitalCommonStock', window );">Additional paid-in capital</a></td>
<td class="nump">2,868,812<span></span>
</td>
<td class="nump">2,215,098<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax', window );">Accumulated other comprehensive loss</a></td>
<td class="num">(30,811)<span></span>
</td>
<td class="num">(32,645)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RetainedEarningsAccumulatedDeficit', window );">Accumulated deficit</a></td>
<td class="num">(2,249,808)<span></span>
</td>
<td class="num">(1,795,911)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquity', window );">Total stockholders' equity</a></td>
<td class="nump">588,351<span></span>
</td>
<td class="nump">386,686<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquity', window );">Total liabilities and stockholders' equity</a></td>
<td class="nump">3,003,675<span></span>
</td>
<td class="nump">2,990,072<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrentAbstract', window );"><strong>Current liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">Convertible senior notes, net</a></td>
<td class="nump">565,026<span></span>
</td>
<td class="nump">562,285<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrentAbstract', window );"><strong>Current liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">Convertible senior notes, net</a></td>
<td class="nump">$ 628,535<span></span>
</td>
<td class="nump">$ 625,380<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after accumulated amortization, of the unamortized liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccountsPayableCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of liabilities incurred (and for which invoices have typically been received) and payable to vendors for goods and services received that are used in an entity's business. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(19)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccountsPayableCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedIncomeTaxesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying amount as of the balance sheet date of the unpaid sum of the known and estimated amounts payable to satisfy all currently due domestic and foreign income tax obligations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(15)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedIncomeTaxesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred and payable, pertaining to costs that are statutory in nature, are incurred on contractual obligations, or accumulate over time and for which invoices have not yet been received or will not be rendered. Examples include taxes, interest, rent and utilities. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after tax, of accumulated increase (decrease) in equity from transaction and other event and circumstance from nonowner source.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-14A<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-11<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480016/944-40-65-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480016/944-40-65-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdditionalPaidInCapitalCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Value received from shareholders in common stock-related transactions that are in excess of par value or stated value and amounts received from other stock-related transactions. Includes only common stock transactions (excludes preferred stock transactions). May be called contributed capital, capital in excess of par, capital surplus, or paid-in capital.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdditionalPaidInCapitalCommonStock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Assets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of asset recognized for present right to economic benefit.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 48<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-48<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 49<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-49<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (bb)<br> -Publisher FASB<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_Assets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AssetsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of asset recognized for present right to economic benefit, classified as current.</p></div>
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210.13-02(a)(4)(iii)(B))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480097/470-10-S99-1B<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480097/470-10-S99-1B<br><br>Reference 19: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480097/470-10-S99-1B<br><br>Reference 20: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481404/852-10-50-7<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AssetsCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetsCurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashAndCashEquivalentsAtCarryingValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of currency on hand as well as demand deposits with banks or financial institutions. Includes other kinds of accounts that have the general characteristics of demand deposits. Also includes short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates. Excludes cash and cash equivalents within disposal group and discontinued operation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483467/210-10-45-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashAndCashEquivalentsAtCarryingValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Aggregate par or stated value of issued nonredeemable common stock (or common stock redeemable solely at the option of the issuer). This item includes treasury stock repurchased by the entity. Note: elements for number of nonredeemable common shares, par value and other disclosure concepts are in another section within stockholders' equity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(22))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerAssetNetCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after allowance for credit loss, of right to consideration in exchange for good or service transferred to customer when right is conditioned on something other than passage of time, classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerAssetNetCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable, classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleDebtCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of the carrying value of long-term convertible debt as of the balance sheet date that is scheduled to be repaid within one year or in the normal operating cycle if longer. Convertible debt is a financial instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(19))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConvertibleDebtCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleDebtNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying amount of long-term convertible debt as of the balance sheet date, net of the amount due in the next twelve months or greater than the normal operating cycle, if longer. The debt is convertible into another form of financial instrument, typically the entity's common stock.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConvertibleDebtNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeRelatedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of the carrying values as of the balance sheet date of obligations incurred through that date and payable for obligations related to services received from employees, such as accrued salaries and bonuses, payroll taxes and fringe benefits. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeRelatedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after valuation and LIFO reserves of inventory expected to be sold, or consumed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483467/210-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Liabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of liability recognized for present obligation requiring transfer or otherwise providing economic benefit to others.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesAndStockholdersEquity">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of liabilities and equity items, including the portion of equity attributable to noncontrolling interests, if any.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesAndStockholdersEquity</td>
</tr>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total obligations incurred as part of normal operations that are expected to be paid during the following twelve months or within one business cycle, if longer.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesCurrentAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermLoansFromBank">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of loans from a bank with maturities initially due after one year or beyond the operating cycle if longer, excluding current portion.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(13)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermLoansFromBank</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseRightOfUseAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's right to use underlying asset under operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseRightOfUseAsset</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAssetsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherAssetsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAssetsNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of noncurrent assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(17))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherAssetsNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of liabilities classified as other, due within one year or the normal operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after accumulated depreciation, depletion and amortization of physical assets used in the normal conduct of business to produce goods and services and not intended for resale. Examples include, but are not limited to, land, buildings, machinery and equipment, office equipment, and furniture and fixtures.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 360<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482099/360-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7A<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-7A<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 360<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478451/942-360-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RetainedEarningsAccumulatedDeficit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated undistributed earnings (deficit).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480016/944-40-65-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480016/944-40-65-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480990/946-20-50-11<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(17))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480008/505-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RetainedEarningsAccumulatedDeficit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShortTermInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investments including trading securities, available-for-sale securities, held-to-maturity securities, and short-term investments classified as other and current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(5))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShortTermInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquity">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of equity (deficit) attributable to parent. Excludes temporary equity and equity attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(31))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 5: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 946<br> -SubTopic 830<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479168/946-830-55-12<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(19))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.6-05(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-2<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(7))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 11: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 12: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 323<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481687/323-10-50-3<br><br>Reference 13: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-28<br><br>Reference 14: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 310<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 4.E)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480418/310-10-S99-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929247920">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares<br></strong></div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityAbstract', window );"><strong>Stockholders' equity:</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockParOrStatedValuePerShare', window );">Common stock, par value (in dollars per share)</a></td>
<td class="nump">$ 0.001<span></span>
</td>
<td class="nump">$ 0.001<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesAuthorized', window );">Common stock, shares authorized (in shares)</a></td>
<td class="nump">300,000,000<span></span>
</td>
<td class="nump">300,000,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="nump">157,908,815<span></span>
</td>
<td class="nump">144,340,526<span></span>
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<td class="nump">157,908,815<span></span>
</td>
<td class="nump">144,340,526<span></span>
</td>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<span></span>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
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<td class="nump">0.00%<span></span>
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<div style="display: none;">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face amount or stated value per share of common stock.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum number of common shares permitted to be issued by an entity's charter and bylaws.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total number of common shares of an entity that have been sold or granted to shareholders (includes common shares that were issued, repurchased and remain in the treasury). These shares represent capital invested by the firm's shareholders and owners, and may be all or only a portion of the number of shares authorized. Shares issued include shares outstanding and shares held in the treasury.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<td style="white-space:nowrap;">us-gaap_CommonStockSharesIssued</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares of common stock outstanding. Common stock represent the ownership interest in a corporation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481112/505-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.6-05(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-2<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 6: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(7))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesAndStockholdersEquityAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929581648">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 705,138<span></span>
</td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostsAndExpensesAbstract', window );"><strong>Expenses:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostOfGoodsAndServicesSold', window );">Cost of sales</a></td>
<td class="nump">11,215<span></span>
</td>
<td class="nump">9,133<span></span>
</td>
<td class="nump">14,116<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ResearchDevelopmentAndPatentExpense', window );">Research, development and patent</a></td>
<td class="nump">901,530<span></span>
</td>
<td class="nump">899,625<span></span>
</td>
<td class="nump">833,147<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SellingGeneralAndAdministrativeExpense', window );">Selling, general and administrative</a></td>
<td class="nump">267,474<span></span>
</td>
<td class="nump">232,619<span></span>
</td>
<td class="nump">150,295<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">1,180,219<span></span>
</td>
<td class="nump">1,141,377<span></span>
</td>
<td class="nump">997,558<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Loss from operations</a></td>
<td class="num">(475,081)<span></span>
</td>
<td class="num">(353,730)<span></span>
</td>
<td class="num">(410,191)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NonoperatingIncomeExpenseAbstract', window );"><strong>Other income (expense):</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentIncomeNet', window );">Investment income</a></td>
<td class="nump">107,022<span></span>
</td>
<td class="nump">89,041<span></span>
</td>
<td class="nump">25,331<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InterestExpense', window );">Interest expense</a></td>
<td class="num">(16,994)<span></span>
</td>
<td class="num">(12,660)<span></span>
</td>
<td class="num">(8,122)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties', window );">Interest expense related to sale of future royalties</a></td>
<td class="num">(73,457)<span></span>
</td>
<td class="num">(68,797)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossOnInvestments', window );">Loss on investments</a></td>
<td class="num">(2,889)<span></span>
</td>
<td class="num">(1,914)<span></span>
</td>
<td class="num">(7,333)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossOnDispositionOfAssets1', window );">Gain (loss) on sale of real estate assets</a></td>
<td class="num">(12)<span></span>
</td>
<td class="num">(161)<span></span>
</td>
<td class="nump">149,604<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherNonoperatingIncomeExpense', window );">Other income (expense)</a></td>
<td class="nump">1,343<span></span>
</td>
<td class="nump">14,256<span></span>
</td>
<td class="num">(7,274)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest', window );">Loss before income tax benefit (expense)</a></td>
<td class="num">(460,068)<span></span>
</td>
<td class="num">(333,965)<span></span>
</td>
<td class="num">(257,985)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Income tax benefit (expense)</a></td>
<td class="nump">6,171<span></span>
</td>
<td class="num">(32,321)<span></span>
</td>
<td class="num">(11,737)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (453,897)<span></span>
</td>
<td class="num">$ (366,286)<span></span>
</td>
<td class="num">$ (269,722)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net loss per share (in dollars per share)</a></td>
<td class="num">$ (3.04)<span></span>
</td>
<td class="num">$ (2.56)<span></span>
</td>
<td class="num">$ (1.9)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Shares used in computing basic net loss per share (in shares)</a></td>
<td class="nump">149,514<span></span>
</td>
<td class="nump">143,190<span></span>
</td>
<td class="nump">141,848<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net loss per share (in dollars per share)</a></td>
<td class="num">$ (3.04)<span></span>
</td>
<td class="num">$ (2.56)<span></span>
</td>
<td class="num">$ (1.9)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net loss per share (in shares)</a></td>
<td class="nump">149,514<span></span>
</td>
<td class="nump">143,190<span></span>
</td>
<td class="nump">141,848<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_CommercialMember', window );">Commercial Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 293,076<span></span>
</td>
<td class="nump">$ 308,591<span></span>
</td>
<td class="nump">$ 303,358<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember', window );">SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">216,090<span></span>
</td>
<td class="nump">240,379<span></span>
</td>
<td class="nump">242,314<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_WainusRoyaltiesMember', window );">WAINUA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">20,207<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_OtherCommercialMember', window );">Other Commercial Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">56,779<span></span>
</td>
<td class="nump">68,212<span></span>
</td>
<td class="nump">61,044<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember', window );">Research and Development Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">412,062<span></span>
</td>
<td class="nump">479,056<span></span>
</td>
<td class="nump">284,009<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_CollaborativeAgreementRevenueMember', window );">Collaborative Agreement Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">332,647<span></span>
</td>
<td class="nump">352,657<span></span>
</td>
<td class="nump">207,222<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_WainuaJointDevelopmentRevenueMember', window );">WAINUA Joint Development Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 79,415<span></span>
</td>
<td class="nump">$ 126,399<span></span>
</td>
<td class="nump">$ 76,787<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of interest expense using the effective interest rate method and amortization of issuance costs related to the sale of future royalties.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ResearchDevelopmentAndPatentExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate costs incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process whether intended for sale or the entity's use, during the reporting period charged to research and development projects. Also includes charges for amortization and write-downs of capitalized patent costs, as well as legal fees for patent litigation and patent defense.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ResearchDevelopmentAndPatentExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostOfGoodsAndServicesSold">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate costs related to goods produced and sold and services rendered by an entity during the reporting period. This excludes costs incurred during the reporting period related to financial services rendered and other revenue generating activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(2)(d))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(2)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostOfGoodsAndServicesSold</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostsAndExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total costs of sales and operating expenses for the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostsAndExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostsAndExpensesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostsAndExpensesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period available to each share of common stock or common unit outstanding during the reporting period and to each share or unit that would have been outstanding assuming the issuance of common shares or units for all dilutive potential common shares or units outstanding during the reporting period.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareDiluted</td>
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<td>na</td>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainLossOnDispositionOfAssets1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) on sale or disposal of assets, including but not limited to property plant and equipment, intangible assets and equity in securities of subsidiaries or equity method investee.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainLossOnDispositionOfAssets1</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainLossOnInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of realized and unrealized gain (loss) on investment.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(9)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(7)(c))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 3: http://www.xbrl.org/2003/role/recommendedDisclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainLossOnInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations, including income (loss) from equity method investments, before deduction of income tax expense (benefit), and income (loss) attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 48<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-48<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 6: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(11))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 9: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 31<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-31<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 235<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477314/942-235-S99-1<br><br>Reference 11: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(10))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 12: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(15))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478524/942-220-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-9<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-8<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-10<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -SubTopic 20<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482659/740-20-45-2<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -SubTopic 10<br> -Topic 235<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InterestExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of interest expense classified as operating and nonoperating. Includes, but is not limited to, cost of borrowing accounted for as interest expense.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 48<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-48<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 49<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-49<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-24<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483013/835-20-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InterestExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</div></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after accretion (amortization) of discount (premium), and investment expense, of interest income and dividend income on nonoperating securities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(7)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(7)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentIncomeNet</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
</div></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
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https://asc.fasb.org/1943274/2147482790/220-10-45-1A<br><br>Reference 36: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-1B<br><br>Reference 37: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478524/942-220-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NonoperatingIncomeExpenseAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NonoperatingIncomeExpenseAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The net result for the period of deducting operating expenses from operating revenues.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 31<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-31<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherNonoperatingIncomeExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of income (expense) related to nonoperating activities, classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(9))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherNonoperatingIncomeExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SellingGeneralAndAdministrativeExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate total costs related to selling a firm's product and services, as well as all other general and administrative expenses. Direct selling expenses (for example, credit, warranty, and advertising) are expenses that can be directly linked to the sale of specific products. Indirect selling expenses are expenses that cannot be directly linked to the sale of specific products, for example telephone expenses, Internet, and postal charges. General and administrative expenses include salaries of non-sales personnel, rent, utilities, communication, etc.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SellingGeneralAndAdministrativeExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The average number of shares or units issued and outstanding that are used in calculating diluted EPS or earnings per unit (EPU), determined based on the timing of issuance of shares or units in the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 16<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482689/260-10-45-16<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of [basic] shares or units, after adjustment for contingently issuable shares or units and other shares or units not deemed outstanding, determined by relating the portion of time within a reporting period that common shares or units have been outstanding to the total time in that period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482689/260-10-45-10<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfSharesOutstandingBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45368025782528">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract', window );"><strong>CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (453,897)<span></span>
</td>
<td class="num">$ (366,286)<span></span>
</td>
<td class="num">$ (269,722)<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Unrealized gains (losses) on investments, net of tax</a></td>
<td class="nump">2,107<span></span>
</td>
<td class="nump">24,484<span></span>
</td>
<td class="num">(24,395)<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Currency translation adjustment</a></td>
<td class="num">(273)<span></span>
</td>
<td class="nump">351<span></span>
</td>
<td class="num">(417)<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTax', window );">Comprehensive loss</a></td>
<td class="num">$ (452,063)<span></span>
</td>
<td class="num">$ (341,451)<span></span>
</td>
<td class="num">$ (294,534)<span></span>
</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax of increase (decrease) in equity from transactions and other events and circumstances from net income and other comprehensive income, attributable to parent entity. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(24))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(26))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478524/942-220-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(22))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-1A<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-1B<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after tax and reclassification adjustment, of gain (loss) in value of unsold investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), attributable to parent.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax, before reclassification adjustments of gain (loss) on foreign currency translation adjustments, foreign currency transactions designated and effective as economic hedges of a net investment in a foreign entity and intra-entity foreign currency transactions that are of a long-term-investment nature.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929590080">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th"><div>Common Stock [Member]</div></th>
<th class="th"><div>Additional Paid in Capital [Member]</div></th>
<th class="th"><div>Accumulated Other Comprehensive Loss [Member]</div></th>
<th class="th"><div>Accumulated Deficit [Member]</div></th>
<th class="th"><div>Total</div></th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquity', window );">Balance at Dec. 31, 2021</a></td>
<td class="nump">$ 141<span></span>
</td>
<td class="nump">$ 1,964,167<span></span>
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<td class="num">$ (32,668)<span></span>
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<td class="num">$ (1,159,903)<span></span>
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<td class="nump">$ 771,737<span></span>
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<td class="nump">141,210<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(269,722)<span></span>
</td>
<td class="num">(269,722)<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(24,395)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(24,395)<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(417)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(417)<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans, net</a></td>
<td class="nump">$ 1<span></span>
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<td class="nump">6,372<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,373<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans, net (in shares)</a></td>
<td class="nump">1,194<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">100,264<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">100,264<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(10,953)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,953)<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)</a></td>
<td class="num">(346)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquity', window );">Balance at Dec. 31, 2022</a></td>
<td class="nump">$ 142<span></span>
</td>
<td class="nump">2,059,850<span></span>
</td>
<td class="num">(57,480)<span></span>
</td>
<td class="num">(1,429,625)<span></span>
</td>
<td class="nump">572,887<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2022</a></td>
<td class="nump">142,058<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(366,286)<span></span>
</td>
<td class="num">(366,286)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">24,484<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">24,484<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">351<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">351<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans, net</a></td>
<td class="nump">$ 2<span></span>
</td>
<td class="nump">49,439<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">49,441<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans, net (in shares)</a></td>
<td class="nump">2,283<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">105,809<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">105,809<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquity', window );">Balance at Dec. 31, 2023</a></td>
<td class="nump">$ 144<span></span>
</td>
<td class="nump">2,215,098<span></span>
</td>
<td class="num">(32,645)<span></span>
</td>
<td class="num">(1,795,911)<span></span>
</td>
<td class="nump">386,686<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2023</a></td>
<td class="nump">144,341<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(453,897)<span></span>
</td>
<td class="num">(453,897)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">2,107<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">2,107<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(273)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(273)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans, net</a></td>
<td class="nump">$ 2<span></span>
</td>
<td class="nump">33,607<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">33,609<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans, net (in shares)</a></td>
<td class="nump">2,068<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueNewIssues', window );">Issuance of public common stock, net</a></td>
<td class="nump">$ 12<span></span>
</td>
<td class="nump">489,108<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">489,120<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesNewIssues', window );">Issuance of public common stock, net (in shares)</a></td>
<td class="nump">11,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">130,999<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">130,999<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquity', window );">Balance at Dec. 31, 2024</a></td>
<td class="nump">$ 158<span></span>
</td>
<td class="nump">$ 2,868,812<span></span>
</td>
<td class="num">$ (30,811)<span></span>
</td>
<td class="num">$ (2,249,808)<span></span>
</td>
<td class="nump">$ 588,351<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2024</a></td>
<td class="nump">157,909<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of decrease to equity for grantee's tax withholding obligation for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase to additional paid-in capital (APIC) for recognition of cost for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 35<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480483/718-10-35-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 13<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481089/718-20-55-13<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481089/718-20-55-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInStockholdersEquityRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-6<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-9<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 805<br> -SubTopic 60<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (g)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147476176/805-60-65-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 323<br> -Name 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</div></td></tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after tax and reclassification adjustment, of gain (loss) in value of unsold investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), attributable to parent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 19<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481231/810-10-45-19<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 20<br> -SubTopic 10<br> -Topic 810<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481231/810-10-45-20<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(3)<br> -SubTopic 10<br> -Topic 810<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481203/810-10-50-1A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax, before reclassification adjustments of gain (loss) on foreign currency translation adjustments, foreign currency transactions designated and effective as economic hedges of a net investment in a foreign entity and intra-entity foreign currency transactions that are of a long-term-investment nature.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares of stock issued as of the balance sheet date, including shares that had been issued and were previously outstanding but which are now held in the treasury.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481112/505-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares used to settle grantee's tax withholding obligation for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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</div></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of new stock issued during the period.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesNewIssues</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:sharesItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number, after forfeiture, of shares or units issued under share-based payment arrangement. Excludes shares or units issued under employee stock ownership plan (ESOP).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481112/505-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480008/505-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<td>xbrli:sharesItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Equity impact of the value of new stock issued during the period. Includes shares issued in an initial public offering or a secondary public offering.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodValueNewIssues</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Value, before forfeiture, of shares issued under share-based payment arrangement. Excludes employee stock ownership plan (ESOP).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross</td>
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<td>duration</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of equity (deficit) attributable to parent. Excludes temporary equity and equity attributable to noncontrolling interest.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquity</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>credit</td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367928359568">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Operating activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (453,897)<span></span>
</td>
<td class="num">$ (366,286)<span></span>
</td>
<td class="num">$ (269,722)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Adjustments to reconcile net loss to net cash used in operating activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Depreciation', window );">Depreciation</a></td>
<td class="nump">9,614<span></span>
</td>
<td class="nump">10,292<span></span>
</td>
<td class="nump">14,328<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense', window );">Amortization of right-of-use operating lease assets</a></td>
<td class="nump">10,040<span></span>
</td>
<td class="nump">9,647<span></span>
</td>
<td class="nump">5,362<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AmortizationOfIntangibleAssets', window );">Amortization of other assets</a></td>
<td class="nump">2,336<span></span>
</td>
<td class="nump">2,559<span></span>
</td>
<td class="nump">2,415<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments', window );">Amortization of premium (discount) on investments, net</a></td>
<td class="num">(37,733)<span></span>
</td>
<td class="num">(28,885)<span></span>
</td>
<td class="nump">7,389<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="nump">6,690<span></span>
</td>
<td class="nump">6,330<span></span>
</td>
<td class="nump">5,373<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPayments', window );">Non-cash royalty revenue related to sale of royalties</a></td>
<td class="num">(44,981)<span></span>
</td>
<td class="num">(44,628)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_InterestExpenseRelatedToSaleOfFutureRoyalties', window );">Non-cash interest related to sale of future royalties</a></td>
<td class="nump">72,846<span></span>
</td>
<td class="nump">68,238<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensation', window );">Stock-based compensation expense</a></td>
<td class="nump">130,200<span></span>
</td>
<td class="nump">105,809<span></span>
</td>
<td class="nump">100,264<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Gain on early retirement of debt</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(13,389)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossOnDispositionOfAssets', window );">Non-cash losses related to disposal of property, plant and equipment</a></td>
<td class="nump">7,404<span></span>
</td>
<td class="nump">16,649<span></span>
</td>
<td class="nump">531<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SaleAndLeasebackTransactionGainLossNet', window );">Loss (gain) on sale of real estate assets</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">161<span></span>
</td>
<td class="num">(150,135)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RealizedInvestmentGainsLosses', window );">Loss on investments</a></td>
<td class="nump">2,892<span></span>
</td>
<td class="nump">1,589<span></span>
</td>
<td class="nump">224<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived', window );">Non-cash losses related to other assets</a></td>
<td class="nump">3,032<span></span>
</td>
<td class="nump">1,661<span></span>
</td>
<td class="nump">2,030<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOperatingCapitalAbstract', window );"><strong>Changes in operating assets and liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerAsset', window );">Contracts receivable</a></td>
<td class="nump">5,590<span></span>
</td>
<td class="num">(72,059)<span></span>
</td>
<td class="nump">36,358<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInInventories', window );">Inventories</a></td>
<td class="num">(5,071)<span></span>
</td>
<td class="num">(2,469)<span></span>
</td>
<td class="nump">5,326<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherOperatingAssets', window );">Other current and long-term assets</a></td>
<td class="num">(25,857)<span></span>
</td>
<td class="num">(33,763)<span></span>
</td>
<td class="num">(27,235)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInAccountsPayable', window );">Accounts payable</a></td>
<td class="nump">15,990<span></span>
</td>
<td class="nump">8,119<span></span>
</td>
<td class="nump">1,094<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable', window );">Income taxes</a></td>
<td class="num">(2,117)<span></span>
</td>
<td class="num">(4,098)<span></span>
</td>
<td class="nump">6,213<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities', window );">Accrued compensation</a></td>
<td class="nump">1,887<span></span>
</td>
<td class="nump">18,549<span></span>
</td>
<td class="nump">10,368<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherCurrentLiabilities', window );">Accrued liabilities and other current liabilities</a></td>
<td class="num">(42,993)<span></span>
</td>
<td class="num">(5,506)<span></span>
</td>
<td class="nump">46,695<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="num">(156,819)<span></span>
</td>
<td class="nump">13,967<span></span>
</td>
<td class="num">(71,248)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInOperatingActivities', window );">Net cash used in operating activities</a></td>
<td class="num">(500,947)<span></span>
</td>
<td class="num">(307,513)<span></span>
</td>
<td class="num">(274,370)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract', window );"><strong>Investing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt', window );">Purchases of short-term investments</a></td>
<td class="num">(1,852,858)<span></span>
</td>
<td class="num">(1,770,814)<span></span>
</td>
<td class="num">(1,485,772)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities', window );">Proceeds from sale of short-term investments</a></td>
<td class="nump">1,769,172<span></span>
</td>
<td class="nump">1,584,676<span></span>
</td>
<td class="nump">989,152<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment', window );">Purchases of property, plant and equipment</a></td>
<td class="num">(45,280)<span></span>
</td>
<td class="num">(23,805)<span></span>
</td>
<td class="num">(15,721)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment', window );">Proceeds from sale of real estate assets</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">22<span></span>
</td>
<td class="nump">254,083<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireIntangibleAssets', window );">Acquisition of licenses and other assets, net</a></td>
<td class="num">(5,061)<span></span>
</td>
<td class="num">(4,206)<span></span>
</td>
<td class="num">(4,378)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInInvestingActivities', window );">Net cash used in investing activities</a></td>
<td class="num">(134,027)<span></span>
</td>
<td class="num">(214,127)<span></span>
</td>
<td class="num">(262,636)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract', window );"><strong>Financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Proceeds from issuance of common stock through equity plans, net</a></td>
<td class="nump">33,609<span></span>
</td>
<td class="nump">49,442<span></span>
</td>
<td class="nump">6,373<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfCommonStock', window );">Proceeds from issuance of common stock in public offering, net</a></td>
<td class="nump">489,120<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfConvertibleDebt', window );">Repayment of 0.125 percent convertible senior notes</a></td>
<td class="num">(44,504)<span></span>
</td>
<td class="num">(487,943)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromConvertibleDebt', window );">Proceeds from issuance of 1.75 percent convertible senior notes</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">575,000<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsOfDebtIssuanceCosts', window );">1.75 percent convertible senior notes issuance costs</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(14,175)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ProceedsFromSaleOfFutureRoyalties', window );">Proceeds from sale of future royalties</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">500,000<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Payments of transaction costs related to sale of future royalties</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,434)<span></span>
</td>
<td class="num">(29)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ProceedsFromRealEstateTransaction', window );">Proceeds from real estate transaction</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">32,352<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfSecuredDebt', window );">Principal payments on mortgage debt</a></td>
<td class="num">(167)<span></span>
</td>
<td class="num">(160)<span></span>
</td>
<td class="num">(50,686)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,953)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivities', window );">Net cash provided by (used in) financing activities</a></td>
<td class="nump">478,058<span></span>
</td>
<td class="nump">644,082<span></span>
</td>
<td class="num">(55,295)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations', window );">Effects of exchange rates on cash</a></td>
<td class="num">(273)<span></span>
</td>
<td class="nump">352<span></span>
</td>
<td class="num">(418)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect', window );">Net increase (decrease) in cash and cash equivalents</a></td>
<td class="num">(157,189)<span></span>
</td>
<td class="nump">122,794<span></span>
</td>
<td class="num">(592,719)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at beginning of year</a></td>
<td class="nump">399,266<span></span>
</td>
<td class="nump">276,472<span></span>
</td>
<td class="nump">869,191<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at end of year</a></td>
<td class="nump">242,077<span></span>
</td>
<td class="nump">399,266<span></span>
</td>
<td class="nump">276,472<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SupplementalCashFlowInformationAbstract', window );"><strong>Supplemental disclosures of cash flow information:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InterestPaidNet', window );">Interest paid</a></td>
<td class="nump">10,869<span></span>
</td>
<td class="nump">6,512<span></span>
</td>
<td class="nump">2,898<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxesPaidNet', window );">Income taxes paid (refunds received)</a></td>
<td class="num">(5,620)<span></span>
</td>
<td class="nump">48,334<span></span>
</td>
<td class="nump">5,010<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract', window );"><strong>Supplemental disclosures of non-cash investing and financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability', window );">Right-of-use assets obtained in exchange for lease liabilities</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">168,931<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CapitalAndPatentExpendituresIncurredButNotYetPaid', window );">Amounts accrued for capital and patent expenditures</a></td>
<td class="nump">$ 947<span></span>
</td>
<td class="nump">$ 172<span></span>
</td>
<td class="nump">$ 4,767<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CapitalAndPatentExpendituresIncurredButNotYetPaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Future cash outflow to pay for purchases of fixed assets and patents that have occurred.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CapitalAndPatentExpendituresIncurredButNotYetPaid</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_InterestExpenseRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of interest expense using the effective interest rate method related to the sale of future royalties.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_InterestExpenseRelatedToSaleOfFutureRoyalties</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow paid to third parties for transaction costs in connection with a monetization transaction of future SPINRAZA and pelacarsen royalties the Company is entitled to under collaboration and licensing agreements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ProceedsFromRealEstateTransaction">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the transfer of legal ownership of two lots of undeveloped land to a real estate investor.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ProceedsFromRealEstateTransaction</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ProceedsFromSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the sale of future royalties under a royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ProceedsFromSaleOfFutureRoyalties</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of royalty payments made during the period under a royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPayments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The sum of the periodic adjustments of the differences between securities' face values and purchase prices that are charged against earnings. This is called accretion if the security was purchased at a discount and amortization if it was purchased at premium. As a noncash item, this element is an adjustment to net income when calculating cash provided by or used in operations using the indirect method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AmortizationOfFinancingCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense attributable to debt issuance costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1F<br> -Subparagraph (b)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1F<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfFinancingCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AmortizationOfIntangibleAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate expense charged against earnings to allocate the cost of intangible assets (nonphysical assets not used in production) in a systematic and rational manner to the periods expected to benefit from such assets. As a noncash expense, this element is added back to net income when calculating cash provided by or used in operations using the indirect method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 350<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482640/350-30-55-40<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 350<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482665/350-30-50-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 350<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482686/350-30-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfIntangibleAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash and cash equivalents, and cash and cash equivalents restricted to withdrawal or usage. Excludes amount for disposal group and discontinued operations. Cash includes, but is not limited to, currency on hand, demand deposits with banks or financial institutions, and other accounts with general characteristics of demand deposits. Cash equivalents include, but are not limited to, short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482913/230-10-50-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-24<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in cash, cash equivalents, and cash and cash equivalents restricted to withdrawal or usage; including effect from exchange rate change. Cash includes, but is not limited to, currency on hand, demand deposits with banks or financial institutions, and other accounts with general characteristics of demand deposits. Cash equivalents include, but are not limited to, short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-24<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -SubTopic 230<br> -Topic 830<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477401/830-230-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Depreciation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of expense recognized in the current period that reflects the allocation of the cost of tangible assets over the assets' useful lives. Includes production and non-production related depreciation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482099/360-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_Depreciation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) from effect of exchange rate changes on cash and cash equivalents, and cash and cash equivalents restricted to withdrawal or usage; held in foreign currencies; including, but not limited to, disposal group and discontinued operations. Cash includes, but is not limited to, currency on hand, demand deposits with banks or financial institutions, and other accounts with general characteristics of demand deposits. Cash equivalents include, but are not limited to, short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 830<br> -SubTopic 230<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477401/830-230-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainLossOnDispositionOfAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) on sale or disposal of property, plant and equipment assets, excluding oil and gas property and timber property.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 360<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482130/360-10-45-5<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 360<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482099/360-10-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainLossOnDispositionOfAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainsLossesOnExtinguishmentOfDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Difference between the fair value of payments made and the carrying amount of debt which is extinguished prior to maturity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481303/470-50-40-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481303/470-50-40-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainsLossesOnExtinguishmentOfDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of impairment loss recognized in the period resulting from the write-down of the carrying amount of a finite-lived intangible asset to fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 350<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482686/350-30-45-2<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 350<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482665/350-30-50-3<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ImpairmentOfIntangibleAssetsFinitelived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxesPaidNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after refund, of cash paid to foreign, federal, state, and local jurisdictions as income tax.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482913/230-10-50-2A<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 23<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-23<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-22<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482913/230-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxesPaidNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInAccountsPayable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the aggregate amount of liabilities incurred (and for which invoices have typically been received) and payable to vendors for goods and services received that are used in an entity's business.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInAccountsPayable</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInContractWithCustomerAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in right to consideration in exchange for good or service transferred to customer when right is conditioned on something other than passage of time.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInContractWithCustomerAsset</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 912<br> -SubTopic 310<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478345/912-310-45-11<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the amounts payable to taxing authorities for taxes that are based on the reporting entity's earnings, net of amounts receivable from taxing authorities for refunds of overpayments or recoveries of income taxes.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInInventories">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the aggregate value of all inventory held by the reporting entity, associated with underlying transactions that are classified as operating activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInInventories</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOperatingCapitalAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOperatingCapitalAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOtherCurrentLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in current liabilities classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOtherCurrentLiabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in employer-related costs classified as other and current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOtherOperatingAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in operating assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOtherOperatingAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InterestPaidNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash paid for interest, excluding capitalized interest, classified as operating activity. Includes, but is not limited to, payment to settle zero-coupon bond for accreted interest of debt discount and debt instrument with insignificant coupon interest rate in relation to effective interest rate of borrowing attributable to accreted interest of debt discount.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 17<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-17<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (e)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-25<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482913/230-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InterestPaidNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInFinancingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow (outflow) from financing activities, including discontinued operations. Financing activity cash flows include obtaining resources from owners and providing them with a return on, and a return of, their investment; borrowing money and repaying amounts borrowed, or settling the obligation; and obtaining and paying for other resources obtained from creditors on long-term credit.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-24<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInFinancingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInInvestingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow (outflow) from investing activities, including discontinued operations. Investing activity cash flows include making and collecting loans and acquiring and disposing of debt or equity instruments and property, plant, and equipment and other productive assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-24<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInInvestingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInOperatingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow (outflow) from operating activities, including discontinued operations. Operating activity cash flows include transactions, adjustments, and changes in value not defined as investing or financing activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-24<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-25<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInOperatingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-6<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-9<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 805<br> -SubTopic 60<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (g)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147476176/805-60-65-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 323<br> -Name 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of periodic reduction over lease term of carrying amount of right-of-use asset from operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsOfDebtIssuanceCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow paid to third parties in connection with debt origination, which will be amortized over the remaining maturity period of the associated long-term debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (e)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsOfDebtIssuanceCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to satisfy grantee's tax withholding obligation for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to acquire investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-11<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-13<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-11<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireIntangibleAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to acquire asset without physical form usually arising from contractual or other legal rights, excluding goodwill.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-13<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquireIntangibleAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow associated with the acquisition of long-lived, physical assets that are used in the normal conduct of business to produce goods and services and not intended for resale; includes cash outflows to pay for construction of self-constructed assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-13<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquirePropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the issuance of a long-term debt instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the additional capital contribution to the entity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfCommonStock</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from issuance of shares under share-based payment arrangement. Includes, but is not limited to, option exercised.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-14<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 718<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from sale, maturity, prepayment and call of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-11<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-11<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the sale of long-lived, physical assets that are used in the normal conduct of business to produce goods and services and not intended for resale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RealizedInvestmentGainsLosses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of realized gain (loss) on investment.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(3)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RealizedInvestmentGainsLosses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow from the repayment of a long-term debt instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfSecuredDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to repay long-term debt that is wholly or partially secured by collateral. Excludes repayments of tax exempt secured debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfSecuredDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase in right-of-use asset obtained in exchange for operating lease liability.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 53<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479589/842-20-55-53<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SaleAndLeasebackTransactionGainLossNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) on sale and leaseback transaction from transfer of asset accounted for as sale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 53<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479589/842-20-55-53<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-4<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479741/842-40-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SaleAndLeasebackTransactionGainLossNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of noncash expense for share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensation</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SupplementalCashFlowInformationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SupplementalCashFlowInformationAbstract</td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367930433120">
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<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical)<br></strong></div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="nump">0.125%<span></span>
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<td class="nump">0.125%<span></span>
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<td class="nump">0.125%<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="re">
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br></p></div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367928717328">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Organization and Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTextBlock', window );">Organization and Significant Accounting Policies</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1. Organization and Significant Accounting Policies</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis of Presentation</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;).</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Organization and Business Activity</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporated in California on January 10, 1989. In conjunction with our IPO, we reorganized as a Delaware corporation in April 1991. We
    were organized principally to develop human therapeutic medicines using antisense technology. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We operate as a <span style="-sec-ix-hidden:Fact_0a919095f48f42f79abafacb21f6d831">single</span> segment, Ionis
    operations, because our chief operating decision maker, or CODM, reviews operating results on an aggregate basis and manages our operations as a single operating segment. Refer to Note 12, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Information</span>, for further details on our segment information.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Use of Estimates</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the United States, or
    U.S., that require us to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue Recognition</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting
    receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include
    the amounts within deferred revenue in our consolidated balance sheets.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities
    performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC,
    Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration
      arrangements within the scope of ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that contain multiple elements, we </span>first<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
      determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC </span>606<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. When we determine elements of a collaboration do not
      reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with
    multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our WAINUA collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue; while
    we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as selling, general and administrative, or SG&amp;A, expense and research and development, or R&amp;D, expense,
    respectively.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of
    revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Identify the contract</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner or customer.</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">2.</span></td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Identify the performance obligations</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the
    contract.</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">3.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Determine the transaction price</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration
      agreement, including any variable consideration.</div>

<div><br/>
    </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">4.</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Allocate the transaction price</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Next, we allocate the transaction price to each of our
        performance obligations. When we have to allocate the transaction price to more than </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligation, we make estimates of the relative stand-alone
        selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do
        not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">5.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Recognize revenue</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize revenue in </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ways, over time or at a point in time. We recognize revenue over time when we are executing on our
        performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a
        specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</span></div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue, which
      in certain cases may require us to estimate our royalty revenue.</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Amendments to Agreements</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the
    accounting for the amendment:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the goods and/or services are sold at a stand-alone selling price.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at
      a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are
      distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment
      to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a
      cumulative-effect adjustment.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Multiple agreements</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to
    determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the agreements were negotiated together with a single objective;</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div>
        </td>

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</table>

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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting
    guidance requires us to account for them as a combined arrangement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative
      Arrangements and Licensing Agreements</span>, for further discussion of our 2018 neurology collaboration with Biogen that included multiple agreements which we negotiated concurrently and in contemplation of one another.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we
      have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts
      receivable to be unconditional. We typically receive payment within </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;quarter of billing our partner or customer</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024,
    approximately 95.6 percent of our contracts receivables were from three significant customers. As of December 31, 2023, approximately 87.8 percent of our contracts receivables were from one
    significant customer.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled Royalties</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our unbilled royalties represent our right to receive consideration from our partners in advance of when we are eligible to bill them for
    royalties. We include these unbilled amounts in other current assets in our consolidated balance sheets.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive
      payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue in our consolidated balance sheets.</span> During the years ended December 31, 2024 and 2023, we recognized $166.1 million and $78.2 million of revenue from
    amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Sales</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs
    and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Patent Expenses</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and
    manufacturing costs, patents and other expenses that are directly related to our R&amp;D operations. We expense R&amp;D costs as we incur them. When we make payments for R&amp;D services prior to the services being rendered, we record those amounts as
    prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in R&amp;D expenses are costs associated with our partner agreements. In 2024, 2023 and 2022, patent expenses were $5.3 million, $4.3 million and $4.7 million, respectively.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities
    for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development
    credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and
    measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight
    of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit
    as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes.
    Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these
    reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the
    provision for income taxes in the period in which we make such determination.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In
    assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We
    base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from
    our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be
    realized. </div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss per Share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We compute basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the
    period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Diluted net loss per share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024,
    2023 and 2022, we incurred a net
    loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss
    per share:</div>

<div><br/>
  </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span>0%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span>0%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Stock Purchase Plan, or ESPP.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024 and 2023, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, would also
    have had an anti-dilutive effect on net loss per share.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">As of December 31, 2024, 2023 and 2022, we had outstanding warrants related to our 0% Notes and 0.125% Notes. We will include the shares issuable
    under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</span> During 2024, 2023 and 2022, the market price
    of our common stock did not exceed the strike price of the warrants.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-Based Compensation Expense</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock
    purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service
    period in our consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated
    multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award
    were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Stock Options and Stock Purchase Rights:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant
    date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the
    awards, and actual and projected employee stock option exercise behaviors. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted
    based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options
    granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this
    change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the years ended December 31, 2024, 2023 and 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we
    gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RSU&#8217;s:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest
    annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. The annual RSUs we granted to our board of directors after June 2020 fully vest after one year. The RSUs we granted to board members at their initial appointment to the board of directors vest annually over a three-year period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PRSU&#8217;s:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added
    PRSU awards to the compensation for our other Section 16 officers. Under the terms of the PRSUs we granted in 2020 through 2022, <span style="-sec-ix-hidden:Fact_65d15117ab79462e81dfb8bbb86a0107"><span style="-sec-ix-hidden:Fact_e9934b85c6af480197be8d0d8b5ea434"><span style="-sec-ix-hidden:Fact_5599af32346c4fce91fa6d27caf4b474">one third</span></span></span>
    of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period
    commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant
    and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third
    anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 150 percent of the target number
    depending on our relative TSR. These PRSU awards also included an alternative three-year payout mechanism, or the Alternative Calculation, under
    which we must calculate an alternative payout at the end of the final three-year measurement period assuming the only measurement period for all
    shares under the award was the three-year period. If the Alternative Calculation is greater than payouts under the sum of the three years, then such PRSU award will pay out to achieve the number of shares payable under the Alternative Calculation.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the PRSUs we granted in 2024 and 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period based on our relative TSR as
    compared to a peer group of companies and as measured at the end of the performance period. Under the terms of the grants, no number of PRSUs is
    guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 200 percent of the target number depending on our relative TSR.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which
    represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Note 8, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Stockholders&#8217; Equity,</span>
    for additional information regarding our stock-based compensation plans.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Concentration of Credit Risk</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term
    investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions,
    corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#8217;s, Standard &amp; Poor&#8217;s, or S&amp;P, or Fitch, respectively. We have established guidelines relative to
    diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value Measurements</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and
    accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1,
    defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly
    traded biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale
    securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments
    from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value
    to the fair value based on observable market prices.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, Cash Equivalents and Investments</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term
    investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for
    identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our consolidated statements of
    operations. We use the specific identification method to determine the cost of securities sold.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have equity investments of less than 20 percent ownership in public and private biotechnology companies that we received as part
      of a technology license or partner agreement. At December 31, 2024, we held equity investments in three publicly traded companies and seven privately held companies.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our consolidated
    statements of operations. We account for our equity investments in publicly traded companies at their listed stock price. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting
    from observable price changes in orderly transactions for the identical or similar investment of the same issuer.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventories</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory in our consolidated balance sheets at the lower of cost or net realizable value under the first-in, first-out
    method, or FIFO. Our inventory costs include material, labor and overhead costs. Our raw materials include active pharmaceutical ingredient, or API, for commercial medicines. We capitalize inventory costs related to drug products when we consider
    future commercialization to be probable and expect to realize future economic benefit. When evaluating whether to capitalize inventory costs, we consider various factors, including the likelihood of receiving required regulatory approvals,
    communications from regulatory agencies such as safety or efficacy concerns, underlying manufacturing processes and supply chain matters, shelf life of the inventory, market trends such as competition and pricing, potential legal matters and potential
    reimbursement strategies. We record inventory costs that do not meet our capitalization requirements as R&amp;D expense in our consolidated statements of operations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated
    net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory and historical write-offs.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Capitalized Materials</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We capitalize the costs of certain materials that we purchase for use in manufacturing our medicines in our clinical development programs
    because until we use these materials, they have alternative future uses. We can use these materials in multiple products and, as a result, each material has future economic value independent of the development status of any single medicine. We include
    capitalized materials in other current assets in our consolidated balance sheets and expense these costs as R&amp;D expenses when the materials are used. We review our capitalized materials periodically for continued alternative future use and reduce
    the carrying value of items in the period in which an impairment is identified.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2024, we reclassified capitalized costs related to materials used in our clinical development programs from inventories to other
    current assets in our consolidated balance sheets. As such, we reclassified the respective prior period amounts to conform with the current year presentation.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which we
    determine as the following (in years):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 80.34%; vertical-align: bottom;"> </td>

    <td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Useful Lives</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software, laboratory, manufacturing and other equipment</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3 to 10</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building, building improvements and building systems</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15 to 40</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land improvements</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leasehold improvements</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 15</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 10</div>
        </td>

  </tr>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived
    assets, which include property, plant and equipment, for impairment whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. We estimate our liability
    for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to third-party clinical management
    costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted
    fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these costs may differ
    materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for each of our convertible debt instruments as a
      single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt
      issuance costs as contra-liabilities in our consolidated balance sheets at issuance and amortize them over the contractual term of the convertible debt instrument using the effective interest rate. </span>The<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> balances of our convertible senior notes presented in our consolidated balance sheets represent the principal balance of each convertible debt instrument less debt issuance costs.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024, we
    had two outstanding convertible senior notes, our 1.75%
    Notes, which mature in June 2028, and our 0% Notes, which mature in April 2026. Our 0.125% Notes matured in December 2024. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and
      Commitments</span>, for further details on our convertible senior notes.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Call Spread</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the issuance of our 0%
    Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of
    purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not
    meet the definition of a liability using the guidance contained in ASC Topic 480; therefore, we account for the note hedges and warrants using the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Derivatives







      and Hedging &#8211; Contracts in Entity&#8217;s Own Equity</span> accounting guidance contained in ASC Topic 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified
    in shareholders&#8217; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our consolidated balance sheets. We reassess our ability to continue to classify any
    outstanding note hedges and warrants in shareholders&#8217; equity at each reporting period. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for
    further details on the call spread transactions. </div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Liability Related to Sale of Future Royalties</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. Under our agreement with Royalty Pharma, we record upfront payments and milestone payments we receive from the sale of future
    royalties as a liability, net of transaction costs. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for further details on the agreement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We record royalty payments made to Royalty Pharma as a reduction of the liability or accrued interest and amortize the transaction costs
    over the estimated life of the royalty stream. We account for the associated interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the
    related product and recognizes the related revenue.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense using our
    current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material
    change in our estimate, we will prospectively adjust the effective interest rate and the related interest expense.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Leases</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use
    operating lease asset and associated short- and long-term operating lease liability in our consolidated balance sheets for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term
    and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we
    will pay over the lease term.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal
    options if we conclude we are reasonably certain to exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease
    term.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information
    available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease.
    Our leases do not include material variable or contingent lease payments. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recent Accounting Standards</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2023, the Financial Accounting Standards Board, or FASB, issued Accounting Standard Update, or ASU, 2023-07, which provides
    updated guidance on segment reporting. The guidance requires public companies to disclose significant expenses that are regularly provided to the CODM, other segment items for each reportable segment and measures of segment profit or loss used by the
    CODM for allocating resources. In addition, the updated guidance requires public companies with a single reportable segment to provide all disclosures required under ASC 280, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Reporting</span>, and public companies to include in interim reports all disclosures related to a reportable segment&#8217;s profit or loss and assets that are currently required in annual reports. This update is effective for
    annual periods beginning after December 15, 2023 and interim periods beginning after December 15, 2024. The guidance is applied on a retrospective basis for all periods presented in the financial statements, unless it is impracticable. We adopted the
    annual reporting requirements in our 2024 Annual Report on Form 10-K. We expect to adopt the interim reporting requirements in our Quarterly Report on Form 10-Q in the first quarter of 2025. Refer to Note 12, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Information</span>, for further details on our segment information.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2023, the FASB issued ASU 2023-09, which provides updated guidance on income tax disclosures. The new guidance requires
    companies to provide additional disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions and
    unrecognized deferred tax liabilities. This update is effective for annual periods beginning after December 15, 2024. Early adoption of this guidance is permitted. The guidance may be applied on a prospective or retrospective basis. We currently plan
    to adopt this guidance in our 2025 Annual Report on Form 10-K.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2024, the FASB issued ASU 2024-03, which requires public companies to disclose disaggregated expenses for certain expenses in
    the income statement. This update is effective for annual periods beginning after December 15, 2026 and interim periods within annual periods beginning after December 15, 2027. Early adoption of this guidance is permitted. The guidance may be applied
    on a prospective or retrospective basis. We are currently assessing the impact and timing of adopting this update.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2024, the FASB issued ASU 2024-04 to clarify the guidance for determining whether to account for early settlements of
    convertible debt as induced conversions or extinguishments. This update is effective for annual periods beginning after December 15, 2025 and interim periods within those annual periods. Early adoption of this guidance is permitted. The guidance may be
    applied on a prospective or retrospective basis. We are currently assessing the impact and timing of adopting this update.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any other recently issued accounting standards to have a material impact to our financial statements or disclosures.</div>
<span></span>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Supplemental Financial Data<br></strong></div></th>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2. Supplemental Financial Data</div>

<div><br/>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventories</div>

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<div style="display:none;"><br/></div>
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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">276</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">154</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,441</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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<div><br/>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>

<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our property, plant and equipment consisted of the following (in thousands):</div>

<div><br/>
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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="background-color: #CCEEFF; vertical-align: bottom; white-space: nowrap; width: 76%;">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86,540</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79,885</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building, building improvements and building systems</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,228</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,228</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leasehold improvements</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,375</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,276</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,855</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,844</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

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    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">191,998</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">159,233</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

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    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>

<div><br/>
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<div style="display:none;"><br/></div>
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<div><br/>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

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    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

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    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">216,090</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">240,379</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">242,314</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,207</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other commercial revenue:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA revenue, net</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,189</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,913</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30,051</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,590</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,299</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30,993</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total other commercial revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56,779</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68,212</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61,044</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293,076</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">308,591</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">303,358</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development revenue:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">332,647</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">352,657</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">207,222</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA joint development revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79,415</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">126,399</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76,787</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">412,062</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">479,056</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">284,009</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: 54pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">705,138</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">787,647</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">587,367</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Revenue Sources</span></span>&#160;</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are sources of revenue and when we typically recognize revenue.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We earn commercial revenue primarily in the form of royalty
      payments on net sales of SPINRAZA and WAINUA. In </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we began earning royalties on net sales of WAINUA.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We earn commercial revenue from TEGSEDI and WAYLIVRA sales
      under our distribution agreements with </span>Sobi<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In addition, we receive royalties from</span> PTC Therapeutics International Limited, or PTC, for TEGSEDI and WAYLIVRA
    sales. Refer to Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, for details on our commercialization partnerships with Sobi and PTC.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also recognize as commercial revenue sales milestone payments and royalties we earn under our other collaborations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In </span>December 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the FDA approved TRYNGOLZA (olezarsen) in the U.S. for the treatment of familial chylomicronemia syndrome, or FCS. Our launch of TRYNGOLZA is currently underway.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaboration agreements</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration
    agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, R&amp;D services and manufacturing services.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the
    effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period,
    relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make
    numerous estimates and may use judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Upfront payments:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we enter into a collaboration agreement and receive an upfront payment, we record the entire upfront payment as deferred revenue if our only performance obligation is for
      R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. If part or all of the upfront payment is a license fee, we recognize as revenue the portion related to the license when
      we deliver the license to our partner because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Milestone payments:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We include variable consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they are
      achieved. We include these milestone payments when they are achieved because there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include regulatory milestone payments in the
      transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting
      rules.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, when we
    achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&amp;D services performance obligation and
    recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone payment to the
    transaction price.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the
    milestone event and we do not have a remaining performance obligation. For example, in 2024, we earned a $10 million milestone payment from
    Biogen when the Ministry of Health, Labour and Welfare of Japan approved Biogen&#8217;s Japanese New Drug Application filing of QALSODY, which we recognized in full because we did not have any remaining performance obligations related to this milestone
    payment.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">License fees:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner because our partner has
      full use of the license and we do not have any additional performance obligations related to the license after delivery.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">WAINUA (Eplontersen) Collaboration with AstraZeneca</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize WAINUA for the
    treatment of transthyretin amyloidosis, or ATTR. Under the terms of the agreement, we received a $200 million upfront payment in 2021. Refer to
    Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, for further details on this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our WAINUA collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the
    co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations
    after we delivered the license to AstraZeneca.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an
    accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#8217;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing WAINUA to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related
    to commercial and medical affairs activities as reductions of our SG&amp;A expense and R&amp;D expense, respectively.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Swedish Orphan Biovitrum AB (Sobi)</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, we concluded that our performance obligation is to provide
    services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global
    commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished
    goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.</div>
<span></span>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931462064">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndLicensingAgreementsAbstract', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CollaborativeArrangementDisclosureTextBlock', window );">Collaborative Arrangements and Licensing Agreements</a></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4. Collaborative Arrangements and Licensing Agreements</div>

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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">AstraZeneca</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">WAINUA (Eplontersen) Collaboration</div>

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  </div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for
    the treatment of ATTR. The FDA and Health Canada approved eplontersen with the brand name, WAINUA, for hereditary ATTR, or ATTRv-PN, while the Medicines and Healthcare products Regulatory Agency, or MHRA, approved WAINUA for ATTRv-PN in the United
    Kingdom, or UK, as WAINZUA. Under the agreement, we are jointly developing WAINUA with AstraZeneca worldwide for ATTRv-PN and ATTR cardiomyopathy, or ATTR-CM. We are jointly commercializing WAINUA with AstraZeneca in the U.S. We granted AstraZeneca
    exclusive rights to commercialize WAINUA outside the U.S.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Over the term of the collaboration, we are eligible to
      receive up to $</span>3.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion, which is comprised of a $</span>200<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment, up to $</span>485<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development and approval milestone payments and up to $</span>2.9<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in sales milestone payments. The agreement includes
      territory-specific development, commercial and medical affairs cost-sharing provisions. In addition, we are eligible to receive up to mid-</span>20 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.S. From inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span>465<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration. We will achieve the next payment of $</span>200<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million or $</span>115<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upon regulatory approval of WAINUA for ATTR-CM in the U.S. or Europe, respectively, under
      this collaboration.</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. As a result, we began earning
    royalties from WAINUA sales, which we recognize as commercial revenue in our consolidated statements of operations.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our WAINUA collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca will perform, (iii) the co-commercialization
    activities that we and AstraZeneca will perform and (iv) the co-medical affairs activities that we and AstraZeneca will perform.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received in 2021. In 2023, we earned a $20 million license fee payment when we licensed rights to Latin America for WAINUA to AstraZeneca. We recognized these payments in full because we did not have any remaining performance obligations after we delivered the
    licenses to AstraZeneca.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration. AstraZeneca is currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we recognize as revenue the 55 percent of cost-share funding AstraZeneca is responsible for in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing WAINUA to market outside the U.S., we recognize cost-share funding we receive from AstraZeneca related to these activities as a reduction of
    our commercial and medical affairs expenses. In the fourth quarter of 2024, we earned a $30 million milestone payment from AstraZeneca when the
    MHRA approved WAINZUA for ATTRv-PN in the UK. We recognized this milestone payment in full as joint development revenue because we did not have any remaining performance obligations related to the milestone payment.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Cardiovascular, Renal and Metabolic Collaboration</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our collaboration for WAINUA, we have a collaboration with AstraZeneca focused on discovering and developing treatments for
    cardiovascular, renal and metabolic diseases, which we formed in 2015. In December 2024, we amended this collaboration agreement with AstraZeneca. The amendment changed future potential milestone payments and royalties we could receive under the
    collaboration. We determined there were no changes that would require adjustments to revenue we previously recognized because we had no ongoing performance obligations under the agreement. Under our collaboration, AstraZeneca has licensed multiple
    medicines from us. AstraZeneca is responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed from us.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $4.3 billion, which is comprised of a $65 million upfront payment, up to $175 million in license fees, up to $514 million
    in development milestone payments, up to $863 million in regulatory milestone payments and up to $2.8 billion in sales milestone payments. In addition, we are eligible to receive tiered royalties up to 10 percent on net sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. From inception through December 31, 2024, we have received more than $340
    million in payments under this collaboration. We will achieve the next payment of up to $30 million if AstraZeneca advances a medicine under this
    collaboration<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for AstraZeneca. We determined the transaction price to be the $65
    million upfront payment we received and we allocated it to our single performance obligation. We recognized revenue for our R&amp;D services performance obligation as we performed services based on our effort to satisfy this performance obligation
    relative to our total effort expected to satisfy our performance obligation. We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> completed our performance obligation in</span> 2021. As we achieved milestone payments for our
    R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. From inception through the completion of our performance obligation, we have included $90 million in payments in the transaction price for our R&amp;D services performance obligation.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance
    obligation. We recognized each of these payments in full in the respective period we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. For example, in the fourth quarter
    of 2024, we earned a $25 million payment when AstraZeneca licensed a compound from us. We recognized this payment in full in 2024 because we did
    not have any remaining performance obligations after we delivered the license to AstraZeneca.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts):</div>

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<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

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    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with AstraZeneca</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">129,759</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">202,236</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79,160</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have any
    deferred revenue from our relationship with AstraZeneca at December 31, 2024 and 2023.</div>

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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Biogen</div>

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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Marketed Medicines</div>

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  </div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2012, we entered into a collaboration agreement with
      Biogen to develop and commercialize SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we received more than $</span>2.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in total payments under this collaboration, including approximately
      $</span>1.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion from SPINRAZA royalties and more than $</span>425<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from R&amp;D revenue. We are receiving tiered royalties ranging
      from </span>11 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span>15 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales of SPINRAZA. We have exclusive in-licensed patents
      related to SPINRAZA from Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on net sales of SPINRAZA. Biogen is responsible for all
      global development, regulatory and commercialization activities and costs for SPINRAZA. We completed our performance obligations under this collaboration in 2016</span>.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2023, we entered into a royalty purchase agreement with Royalty Pharma in which Royalty Pharma receives 25 percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to 45 percent of royalty payments in 2028, on up to $1.5 billion in annual
    sales. Royalty Pharma&#8217;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $475
    million or $550 million, depending on the timing and occurrence of the U.S. Food and Drug Administration, or FDA, approval of pelacarsen, which
    Novartis is developing. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for further discussion of this agreement.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">QALSODY</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2018, Biogen exercised its option to license QALSODY, our medicine that received accelerated approval from the FDA in April 2023 and
    marketing authorization under exceptional circumstances from the European Medicines Agency, or EMA, in May 2024 for the treatment of adult patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS. As a result, Biogen is
    responsible for global development, regulatory and commercialization activities and costs for QALSODY. Biogen is also evaluating QALSODY as a potential treatment for presymptomatic SOD1-ALS patients in the ongoing ATLAS study. From inception through December 31, 2024, we received more than $110
    million in total payments under this collaboration, including approximately $3 million from QALSODY royalties and $108 million from R&amp;D revenue. We are receiving tiered royalties ranging from 11 percent to 15 percent on net sales of QALSODY. We completed our
    performance obligations under this collaboration in 2020.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">New Antisense Medicines for the Treatment of SMA</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2017, we entered into a collaboration agreement with
      Biogen to </span>identify <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense medicines for the treatment of SMA</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At the commencement of this collaboration, we received a </span>$25 million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> upfront payment from Biogen. In </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2021</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Biogen exercised its option to license ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">306</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, a drug we discovered under this collaboration, for which </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">we earned a $</span>60<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee payment. We recognized this payment as revenue in full because</span> Biogen had full use of the license without any continuing involvement from us. Biogen is solely responsible for the costs and
    expenses related to the development, manufacturing and potential future commercialization of ION306 following the option exercise. We do not have any remaining performance obligations under this collaboration. <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We will receive development and regulatory milestone payments from Biogen if new medicines, including ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">306</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, advance towards marketing approval.</span></div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $555 million if Biogen advances ION306, which is comprised of up to $45
    million in development milestone payments, up to $110 million in regulatory milestone payments and up to $400 million in sales milestone payments. In addition, we are eligible to receive tiered royalties <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">from the mid-teens to </span>mid-20 percent range <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">on net sales from any product that Biogen successfully commercializes under this collaboration.</span> From inception through December 31, 2024, we received $85 million in payments under this
    collaboration. We will achieve the next payment of up to $45 million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">if Biogen initiates a Phase 3 trial under this collaboration.</span></div>

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  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Neurology Collaborations</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have multiple collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders,
    including our 2018 and 2012 neurology collaborations. Under these collaborations, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for certain neurological diseases and the option to license certain medicines
    resulting from these collaborations. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our 2018 neurology collaboration, we are currently advancing multiple programs. For each medicine under this collaboration, we are
    eligible to receive <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">up to $</span>270<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is comprised of a $</span>15<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee, up to $</span>105<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestone payments and up to $</span>150<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone payments</span>. In addition, we are eligible to receive tiered royalties up to
    the 20 percent range on net sales from any product that Biogen successfully commercializes under this collaboration. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received nearly $</span>1.1<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in payments under this collaboration, including payments to purchase our stock. </span>We will achieve the next payment of up to $15 million if Biogen licenses a medicine under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of our 2018 neurology collaboration, we determined our transaction price to be $552 million, comprised of $375 million from the upfront payment and $177 million for the premium paid by Biogen for its purchase of our common stock. We allocated the transaction price to our single performance obligation,
    which was to perform R&amp;D services for Biogen. From inception through December 31, 2024, we have included $623 million in upfront and milestone payments in the transaction price for our R&amp;D services performance obligation. We recognize revenue for our R&amp;D
    services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance
    obligation at the end of the contractual term in June 2028.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our 2012 neurology collaboration, Biogen exercised its option to license IONIS-MAPT<sub>Rx</sub>, an investigational RNA-targeted
    medicine for the potential treatment of Alzheimer&#8217;s disease, or AD, in 2019. As a result, Biogen is responsible for global development, regulatory and commercialization activities and costs for IONIS-MAPT<sub>Rx</sub>. We are eligible to receive up to
    $185 million for the IONIS-MAPT<sub>Rx</sub> program, which is comprised of a license fee of $45 million, up to $10 million in development milestone payments and up to
    $130 million in regulatory milestone payments, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. In addition, we are eligible to
    receive tiered royalties up to the mid-teens on net sales of any medicines resulting from the IONIS-MAPT<sub>Rx</sub> program. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span>230<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration. </span>We will achieve the
    next payment of $25 million if Biogen advances MAPT<sub>Rx</sub> into Phase 3 development under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of our 2012 neurology collaboration, we identified two separate performance obligations as our development work for IONIS-MAPT<sub>Rx</sub> and ION582. We completed our R&amp;D services performance obligations for IONIS-MAPT<sub>Rx</sub>
    and ION582 in 2022 and 2024, respectively. From inception through the completion of our performance obligations, we have included $57 million in
    the transaction price for our IONIS-MAPT<sub>Rx</sub> development performance obligation. From inception through the completion of our performance obligations, we have included $68 million in milestone payments in the transaction price for our ION582 development performance obligation. We recognized revenue for our R&amp;D services performance obligations
    as we performed services based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the second quarter of 2024, Biogen&#8217;s option to license ION582, an investigational antisense medicine for the potential treatment of
    Angelman syndrome, or AS, expired unexercised. As a result, we recognized $30 million of R&amp;D revenue from previously deferred milestone
    payments related to the ION582 study because we did not have any remaining performance obligations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Biogen</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">368,058</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">350,146</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">366,696</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span>211.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>307.4<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, from our relationship with Biogen.</span></div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">GSK</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2010, we entered into a collaboration with GSK using our antisense drug discovery platform to discover and develop new medicines
    against targets for serious and rare diseases, including infectious diseases. Upon initiating the collaboration, we received an upfront payment of $35
    million. Under our collaboration, GSK is developing bepirovirsen for the treatment of chronic hepatitis B virus infection, or HBV, infection. In 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global
    development, regulatory and commercialization activities and costs for the HBV program.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive nearly $260 million, which is comprised of a $25 million license fee, up to $42.5 million in development milestone payments, up to $120
    million in regulatory milestone payments and up to $70 million in sales milestone payments if GSK successfully develops and commercializes
    bepirovirsen. In addition, we are eligible to receive tiered royalties up to the low-teens on net sales of bepirovirsen. From inception through December 31, 2024, we have received more than $105 million in an upfront payment and payments related to the HBV program.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We completed our R&amp;D services performance obligations in 2015. Therefore, we do not have any remaining performance obligations under
    our collaboration with GSK. However, we can still earn additional payments and royalties as GSK advances the HBV program.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> In 2023, we earned a $</span>15<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment when GSK initiated a Phase 3 program of
      bepirovirsen. We recognized this milestone payment as R&amp;D revenue in full in 2023 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next payment of $</span>15<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if the FDA accepts an NDA filing of bepirovirsen for review.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with GSK (in thousands, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with GSK</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,000</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have any
    deferred revenue from our relationship with GSK at December 31, 2024 and 2023.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Novartis</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Pelacarsen Collaboration</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2017, we initiated a collaboration with Novartis to
      develop and commercialize pelacarsen.</span> Novartis is responsible for conducting and funding development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study that Novartis initiated in 2019.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $900 million, which is comprised of a $75 million upfront payment, a $150 million license fee, a $25 million
    development milestone payment, up to $290 million in regulatory milestone payments and up to $360 million in sales milestone payments. We are also eligible to receive tiered royalties in the mid-teens to low 20 percent range on net sales of pelacarsen. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span>275<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration. We</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> will achieve the next payment of $</span>50<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if the FDA accepts an NDA filing for pelacarsen.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At the commencement of this collaboration, </span>we
    determined our transaction price to be $108.4 million, comprised of the $75 million from the upfront payment, $28.4 million for the premium paid
    by Novartis for its purchase of our common stock and $5.0 million for the potential premium Novartis would have paid if they purchased our common
    stock in the future. We <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">identified </span>four<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> separate performance obligations as the R&amp;D services and API for pelacarsen and olezarsen. We recognized revenue for our R&amp;D services performance obligations as we
      performed services </span>based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>We
    completed our R&amp;D services performance obligations for olezarsen and pelacarsen<sub>&#160;</sub>in 2019. As such, we recognized all revenue we allocated to the olezarsen and pelacarsen<sub>&#160;</sub>R&amp;D services as of the end of 2019. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through the completion of our performance obligations, we have included $</span>104<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments in the transaction price for our R&amp;D services performance obligations under this collaboration.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As described in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Biogen SPINRAZA</span>
    section above, in 2023, we entered into a royalty purchase agreement with Royalty Pharma. Under the agreement, in addition to a minority interest in SPINRAZA royalties, Royalty Pharma will receive 25 percent of any future royalty payments on pelacarsen. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term
      Obligations and Commitments</span>, for further discussion of this agreement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">New Medicine for the Treatment of Lp(a)-Driven Cardiovascular Disease</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2023, we entered into a collaboration and license agreement with Novartis for the discovery, development and commercialization
    of a novel medicine for patients with Lp(a)-driven cardiovascular disease, or lipoprotein(a)-driven CVD. Novartis is solely responsible for the development, manufacturing and potential commercialization of the next generation Lp(a) therapy.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $730 million, which is comprised of a $60 million upfront payment, up to $155 million in development milestone payments, up to $105
    million in regulatory milestone payments and up to $410 million in sales milestone payments. In addition, we are eligible to receive tiered
    royalties ranging from 10 percent to 20 percent
    on net sales. From inception through December 31, 2024, we have received more than $65 million from payments under this collaboration. We will achieve the next payment of $10
    million if Novartis advances a medicine under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At the commencement of this collaboration, we identified </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligation, which was to perform R&amp;D services for Novartis.
    </span>We recognized revenue for our R&amp;D services performance obligation as we performed services based on our effort to satisfy this performance obligation relative to our total effort expected to satisfy our performance obligation. We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> completed our performance obligation in</span> the third quarter of 2024. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction
    price for our R&amp;D services performance obligation.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> From inception through the completion of our performance obligation, we have included $</span>65<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in upfront and milestone payments in the transaction price for our
      R&amp;D services performance obligation under this collaboration.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Novartis (in thousands, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Novartis</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37,762</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30,194</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">237</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less than 1%</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our consolidated balance sheets at December 31, 2024 and 2023 included deferred revenue of $4.2 million and $30.0 million, respectively, from our relationship with Novartis.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Roche</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Sefaxersen
      (IONIS-FB-L</span><sub>Rx</sub><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">) for Complement-Mediated Diseases</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2018, we entered into a collaboration agreement with Roche to<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop sefaxersen (IONIS-FB-L</span><sub>Rx</sub>) for the treatment of complement-mediated diseases, including immunoglobulin A nephropathy, or IgAN, and geographic atrophy, or GA. In April 2023, Roche initiated a
    Phase 3 study of sefaxersen in patients with IgAN.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">After positive data from a Phase 2 clinical study in patients
      with IgAN, </span>Roche<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> licensed </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">sefaxersen</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2022</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for $</span>35<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. As a result, Roche is responsible for global development, regulatory and commercialization activities, and costs for sefaxersen. In 2022, we amended our sefaxersen
      collaboration agreement with Roche. The amendment changed future potential milestone payments we could receive under the collaboration. We determined there were no changes that would require adjustments to revenue we previously recognized.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In </span>July 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Roche discontinued development of </span>sefaxersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of GA, following the completion of the Phase </span>2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> study, which showed a favorable safety profile and target engagement, but insufficient efficacy to advance into Phase </span>3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> development.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Over the term of the </span>sefaxersen <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">collaboration for the treatment of IgAN, we are eligible to receive up to $</span>430<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is comprised of a $</span>35<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee, up to $</span>25<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestone payments, up to $</span>90<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone payments and up to $</span>280<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in sales milestone payments. In addition, we are also eligible to receive tiered royalties from the high teens to </span>20 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales.</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>From inception
    through December 31, 2024, we have received more than $140 million in payments under this collaboration. <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We will achieve the next payment of $</span>23.5<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if Roche advances sefaxersen for the
      treatment of IgAN under this collaboration.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Roche. We recognized revenue for our R&amp;D services performance obligation as we performed services based on our effort to satisfy this performance
    obligation relative to our total effort expected to satisfy our performance obligation. We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> completed our performance obligation in</span> the fourth quarter of 2024. As we
    achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. From inception through the completion of our performance obligation, we have included $97 million in upfront and milestone payments in the transaction price for our R&amp;D services performance obligation under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Huntington&#8217;s Disease</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2013, we entered into an agreement with Hoffmann-La Roche Inc and F. Hoffmann-La Roche Ltd, collectively Roche, to develop treatments
      for Huntington&#8217;s disease, or HD, based on our antisense technology. Under the agreement, we discovered and developed tominersen, an investigational medicine targeting HTT protein. We developed tominersen through completion of our Phase 1/2 clinical
      study in people with early-stage HD. In 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. As a result, Roche is responsible for all global development, regulatory and commercialization activities and
      costs for tominersen.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $395 million, which is comprised of a $30 million upfront payment, a $45 million license fee, up to $70 million in
    development milestone payments, up to $170 million in regulatory milestone payments and up to $80 million in sales milestone payments as tominersen advances. In addition, we are eligible to receive up to $136.5 million in milestone payments for each additional medicine successfully developed. We are also eligible to receive tiered royalties up to the mid-teens on net sales of any
    product resulting from this collaboration. From inception through December 31, 2024, we have received more than $150 million in payments under this collaboration. We will achieve the next payment of $17.5 million if Roche advances a medicine under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $30
    million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation.
    We recognized revenue for our R&amp;D services performance obligation over our period of performance, which ended in 2017.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance
    obligation. We recognized each of these payments in full in the respective period in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In 2021, Roche decided to
    discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest HD based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded independent data monitoring committee, or iDMC.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2023, Roche initiated the Phase 2, GENERATION HD2, study of tominersen in patients with prodromal or early manifest HD. Roche is
    focusing on early-stage and younger patients based on the post-hoc analyses from the GENERATION HD1 study that suggested tominersen may benefit these patient groups. We do not have any remaining performance obligations related to tominersen under this
    collaboration with Roche; however, we can still earn additional payments and royalties as Roche advances tominersen.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RNA-Targeting Medicines for Alzheimer&#8217;s Disease and Huntington&#8217;s Disease</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2023, we entered into an agreement with Roche to develop two undisclosed early-stage programs for RNA-targeting investigational medicines for the treatment of AD and HD. Under the agreement, we are responsible for advancing the two programs through preclinical studies and Roche is responsible for clinical development, manufacturing and commercialization of the medicines if they
    receive regulatory approval.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $625 million, which is comprised of a $60 million upfront payment, up to $167 million in development milestone payments and up to $398
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales. From inception through December 31, 2024, we have received more than $60 million in payments under this collaboration. We will achieve the next payment of $7.5 million if we advance a medicine under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We identified two performance
    obligations under this new agreement, comprised of R&amp;D services for each of the two separate programs. We determined the transaction price
    to be the $60 million upfront payment we received in the fourth quarter 2023. We allocated the transaction price based on the estimated
    stand-alone selling price of each performance obligation as follows:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$45 million for the R&amp;D services for the investigational
            medicine for AD; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</span>15<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the R&amp;D services for t</span>he investigational medicine for HD.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are recognizing revenue for our R&amp;D services
      performance obligations as we perform services based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations. </span>We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> completed our performance obligation for the investigational medicine for AD in June 2024. We currently estimate we will satisfy our performance obligation for the investigational medicine HD at the end of the research term of
      July 2025.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Roche (in thousands, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Roche</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,871</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48,838</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67,202</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span>7.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>36.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, from our relationship with Roche.</span></div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Commercialization Partnerships</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Otsuka</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2023, we entered into an agreement with Otsuka Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe.
    In the second quarter of 2024, we expanded the agreement to include commercialization rights for donidalorsen in the Asia-Pacific region. As a result, we received a $20 million upfront payment from Otsuka. We are responsible for the ongoing development of donidalorsen. We retained the rights to commercialize donidalorsen in the U.S. and in the rest of the world, assuming regulatory
    approval.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of this collaboration, we are eligible to receive up to $290 million, which is comprised of $85 million in upfront payments, up to
    $65 million in regulatory milestone payments and up to $140 million in sales milestone payments. In addition, we are eligible to receive tiered royalties up to 30 percent
    on net sales. In the fourth quarter of 2024, we earned a $15 million milestone payment from Otsuka when the EMA accepted our Marketing
    Authorization Application, or MAA, filing for donidalorsen in the European Union, or EU. We will achieve the next payment of $15 million if the
    European Commission approves donidalorsen under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We identified two performance
    obligations under this agreement, comprised of our license of donidalorsen to Otsuka and R&amp;D services for donidalorsen. We determined the transaction price to be $85 million, comprised of the following:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$65 million from the upfront payment we received in 2023; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$20 million from the upfront payment we received in 2024.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$73.5 million for the license of donidalorsen; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$11.5 million for the R&amp;D services for donidalorsen.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our
    performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligations in March 2026.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2024, we entered into an agreement with Otsuka to commercialize ulefnersen worldwide. We are responsible for the ongoing
    development of ulefnersen.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From inception through December 31, 2024,
    we have received more than $95 million in payments under these collaborations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the year ended December 31, 2024, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amount):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Otsuka</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46,856</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56,480</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span>6.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>8.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, from our relationship with Otsuka.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PTC Therapeutics</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2018, we entered into an exclusive license agreement with
      PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries. Under the license agreement, we are eligible to receive royalties from PTC in the mid-</span>20 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> range on net sales for each medicine. </span>In December 2021 and September 2023, we
    started receiving royalties from PTC for TEGSEDI and WAYLIVRA sales, respectively<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Swedish Orphan Biovitrum AB (Sobi)</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2021, we began commercializing TEGSEDI and WAYLIVRA in
      Europe and TEGSEDI in North America through distribution agreements with Sobi. </span>Under our distribution agreements, Sobi is responsible for commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. We are
    responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. Under our agreements with Sobi, Sobi does not generally have a right of return. We recognize as revenue the price Sobi
    pays us for the inventory when we deliver the finished goods inventory to Sobi. In addition, we earn a distribution fee on net sales from Sobi for each medicine.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2023, our distribution agreement for TEGSEDI in North America was terminated and Sobi began transitioning responsibilities to
    us. Following the transition, we discontinued TEGSEDI in North America in 2024. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">During the years ended December 31, 2024, 2023 and 2022, we earned nominal revenue from our
      distribution agreement with Sobi for TEGSEDI in North America.</span></div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Technology Enhancement Collaborations</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bicycle Therapeutics</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2020, we entered into a collaboration agreement with Bicycle and <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">obtained an option to license its peptide technology that we expect can expand our LICA platform to target both skeletal and cardiac muscle, and potentially deliver medicines across the blood brain barrier</span>. In 2021, we paid $42 million when we exercised our option to license Bicycle&#8217;s technology, which included an equity investment in Bicycle. As part of our stock purchase, we
    entered into a lockup agreement with Bicycle that restricted our ability to trade our Bicycle shares for one year. In 2021, we recorded a $7.2 million equity investment for the shares we received in Bicycle. We recognized the remaining $34.8 million as R&amp;D expense in 2021. W<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e will pay Bicycle milestone payments and royalties that are
      contingent on the achievement of certain development, regulatory and sales events.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Metagenomi</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, we entered into a collaboration and license agreement with Metagenomi to research, develop and commercialize investigational
    medicines for up to four initial genetic targets, and, upon the achievement of certain development milestones, four additional genetic targets using gene editing technologies. As a result, we paid $80 million to license Metagenomi&#8217;s technologies and will pay Metagenomi certain fees for the selection of genetic targets. We recorded the $80 million payment as R&amp;D expense in 2022 upon receiving a license from Metagenomi for intellectual property that is in research with no current alternate use. In addition, we
    will pay Metagenomi milestone payments and royalties that are contingent on the achievement of certain development, regulatory and sales events. We will also reimburse Metagenomi for certain of its costs in conducting its research and drug discovery
    activities under the collaboration.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Other Agreements</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Alnylam Pharmaceuticals, Inc.</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of our agreement with Alnylam, we co-exclusively (with ourselves) licensed to Alnylam our patent estate relating to
      antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics, with Alnylam having the exclusive right to grant platform sublicenses for double-stranded RNAi. In exchange for such rights, we are eligible to earn
      a technology access fee, participate in fees from Alnylam&#8217;s partnering programs and earn future milestone and royalty payments from Alnylam. We retained exclusive rights to our patents for single-stranded antisense therapeutics and for a limited
      number of double-stranded RNAi therapeutic targets and all rights to single-stranded RNAi, or ssRNAi, therapeutics. In turn, Alnylam nonexclusively licensed to us its patent estate relating to antisense motifs and mechanisms and oligonucleotide
      chemistry to research, develop and commercialize single-stranded antisense therapeutics, ssRNAi therapeutics, and to research double-stranded RNAi compounds. We also received a license to develop and commercialize double-stranded RNAi therapeutics
      targeting a limited number of therapeutic targets on a nonexclusive basis. Additionally, in 2015, we and Alnylam entered into an alliance in which we cross-licensed intellectual property. Under this alliance, we and Alnylam each obtained exclusive
      license rights to four therapeutic programs. Alnylam granted us an exclusive, royalty-bearing license to its chemistry, RNA targeting
      mechanism and target-specific intellectual property for oligonucleotides against four targets, including FXI and Apo(a) and two other targets. In exchange, we granted Alnylam an exclusive, royalty-bearing license to our chemistry, RNA targeting mechanism and target-specific
      intellectual property for oligonucleotides against four other targets. Alnylam also granted us a royalty-bearing, non-exclusive license to new
      platform technology arising from May 2014 through April 2019 for single-stranded antisense therapeutics. In turn, we granted Alnylam a royalty-bearing, non-exclusive license to new platform technology arising from May 2014 through April 2019 for
      double-stranded RNAi therapeutics.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022, we earned the following revenue from our relationship with Alnylam (in thousands, except percentage amounts):</div>

<div><br/>
    </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Alnylam</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,110</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,426</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,389</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have any
    deferred revenue from our relationship with Alnylam at December 31, 2024 and 2023.</div>
<span></span>
</td>
</tr>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931466992">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments<br></strong></div></th>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5. Investments</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2024:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">One year</span>
            or less</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">one year</span>
            but within <span style="text-indent: 0pt;">two years</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">two years</span>
            but within <span style="text-indent: 0pt;"><span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30">three and a half years</span></span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As illustrated above, at December 31, 2024,
    93 percent of our available-for-sale securities had a maturity of less than two years.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these
    securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We invest in debt securities with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp;
    Poor&#8217;s, Moody&#8217;s or Fitch, respectively.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At December 31, 2024, we had an ownership interest of less than 20 percent </span>in seven
    private companies and three public companies with which we conduct business<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2024</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">593,810</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">487</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(240</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">594,057</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143,647</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">287</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(39</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143,895</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">657,285</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">825</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(120</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">657,990</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,516</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,524</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,402,258</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,607</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(399</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,403,466</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">439,561</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">723</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,275</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">438,009</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,255</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(289</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,103</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">149,086</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">124</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(476</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">148,734</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">698</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">696</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">654,600</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">984</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,042</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">652,542</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,056,858</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,591</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,441</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,056,008</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,660</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Privately held equity securities included in deposits and other assets (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,115</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,001</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,093</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35,012</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,027</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(13,753</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46,286</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,091,870</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,618</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(17,194</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,102,294</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2023</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">559,967</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">157</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,625</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">557,499</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">224,711</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(611</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">224,164</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">513,784</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">152</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,889</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">512,047</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,757</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(113</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,686</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,316,219</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">415</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,238</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,311,396</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">243,151</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,270</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(692</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">243,729</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">110,138</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">547</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(21</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">110,664</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">294,873</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,239</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(480</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">295,632</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,466</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,469</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">651,628</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,063</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,197</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">653,494</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,967,847</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,478</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,435</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,964,890</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">236</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,832</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,301</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Privately held equity securities included in deposits and other assets (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,115</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,001</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,125</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42,991</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35,012</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,237</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,957</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49,292</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,002,859</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,715</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(17,392</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,014,182</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Includes investments classified as cash equivalents in our consolidated
            balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our publicly traded equity securities are included in other current
            assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2024, we recorded a $1.0 million net <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">unrealized loss in our consolidated statement of
              operations related to changes in the fair value of our investments in publicly traded companies.</span></div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at</span> cost minus impairments, plus or minus changes resulting from observable price changes in
            orderly transactions for the identical or similar investment of the same issuer, which are Level 3 inputs. In the year ended December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recorded a $</span>2.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million net unrealized loss in our consolidated statements of operations related to observable price changes of our investments in privately held companies.</span></div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our investments we considered to be temporarily impaired at&#160;</span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;(in thousands, except for number of investments):</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Temporary</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">274</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">488,949</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,463</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,713</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(52</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">516,662</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,515</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67,854</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(328</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67,854</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(328</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">252,926</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(503</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,173</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(93</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">277,099</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(596</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">696</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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        </td>

  </tr>

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          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">346</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">811,068</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,296</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52,015</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(145</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">863,083</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,441</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates
    since purchase rather than underlying credit deterioration for any of the issuers. We believe it is more likely than not that we will be able to hold our debt securities with declines in value to maturity. Therefore, we intend to hold these securities
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6. Fair Value Measurements</div>

<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at December 31, 2024 and 2023&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective
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<div><br/>
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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2024</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">180,445</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">180,445</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,032,066</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,032,066</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">208,998</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">208,998</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">806,724</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">806,724</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,524</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,524</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">696</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">696</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (3)</div>
          </div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,241,716</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">992,432</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,249,284</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">185,424</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">185,424</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (4)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">801,228</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">801,228</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">334,828</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">334,828</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">807,679</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">807,679</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,155</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,155</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (3)</div>
          </div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,301</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,301</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,156,615</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">999,404</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,157,211</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in cash and cash equivalents in our consolidated balance
            sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in short-term investments in our consolidated balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in other current assets in our consolidated balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$33.0 million was included in cash and cash equivalents, with the difference included in short-term investments in our consolidated balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Convertible Notes</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our 1.75% Notes and 0% Notes had a fair value of $569.3 million and $612.8 million at December 31, 2024,
    respectively. Our 1.75% Notes, 0%
    Notes and 0.125% Notes had a fair value of $661.1
    million, $667.8 million and $42.4
    million at December 31, 2023, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are
    Level 2 measurements because the notes do not trade regularly.</div>
<span></span>
</td>
</tr>
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<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for the fair value of financial instruments (as defined), including financial assets and financial liabilities (collectively, as defined), and the measurements of those instruments as well as disclosures related to the fair value of non-financial assets and liabilities. Such disclosures about the financial instruments, assets, and liabilities would include: (1) the fair value of the required items together with their carrying amounts (as appropriate); (2) for items for which it is not practicable to estimate fair value, disclosure would include: (a) information pertinent to estimating fair value (including, carrying amount, effective interest rate, and maturity, and (b) the reasons why it is not practicable to estimate fair value; (3) significant concentrations of credit risk including: (a) information about the activity, region, or economic characteristics identifying a concentration, (b) the maximum amount of loss the entity is exposed to based on the gross fair value of the related item, (c) policy for requiring collateral or other security and information as to accessing such collateral or security, and (d) the nature and brief description of such collateral or security; (4) quantitative information about market risks and how such risks are managed; (5) for items measured on both a recurring and nonrecurring basis information regarding the inputs used to develop the fair value measurement; and (6) for items presented in the financial statement for which fair value measurement is elected: (a) information necessary to understand the reasons for the election, (b) discussion of the effect of fair value changes on earnings, (c) a description of [similar groups] items for which the election is made and the relation thereof to the balance sheet, the aggregate carrying value of items included in the balance sheet that are not eligible for the election; (7) all other required (as defined) and desired information.</p></div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367930225312">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtDisclosureAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtDisclosureTextBlock', window );">Long-Term Obligations and Commitments</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Long-Term Obligations and Commitments</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The carrying value of our long-term obligations was as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">1.75</span>%
            convertible senior notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">565,026</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">562,285</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">0</span>%
            convertible senior notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">628,535</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">625,380</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">542,212</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">513,736</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">170,869</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,969</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mortgage debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,714</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,859</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other obligations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43,425</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,714</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,958,781</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,922,943</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: current portion</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,279</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(8,831</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total Long-Term Obligations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,949,502</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,914,112</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2023, our 0.125%
    Notes was classified as a current liability because they matured in December 2024.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt and Call Spread</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1.75 Percent
    Convertible Senior Notes</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2023, we completed a $575.0
    million offering of our 0.125% Notes and used $488.2
    million of the net proceeds from the issuance of the 1.75% Notes to repurchase $504.4 million in principal of our 0.125% Notes. In December 2024, we
    used $44.5 million of the net proceeds to settle the remaining principal balance of our 0.125% Notes upon maturity.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2024, we had the
    following 1.75% Notes outstanding (in millions, except interest rate and price per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.75% Notes</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">575.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_6bfb094eab7041389566a848570cbbe5">June 2028</span></div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.75</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.73</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">0 Percent
    Convertible Senior Notes and Call Spread</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we completed a $632.5
    million offering of our 0% Notes. We used $319.0
    million of the net proceeds from the issuance of our 0% Notes to pay the remaining $309.9 million principal balance of our 1% convertible senior notes, or 1% Notes, in 2021.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2024, we had the
    following 0% Notes outstanding (in millions, except interest rate and price per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">0% Notes</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_77100aa329424b42b6f03dc4fa1e2472">April 2026</span></div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.84</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.39</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and
    selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% Notes by increasing the effective conversion
    price on our 0% Notes. We increased our effective conversion price to $76.39 with the same number of underlying shares as our 0% Notes. The
    call spread cost us $46.9 million, of which $136.7
    million was for the note hedge purchase, offset by $89.8 million we received for selling the warrants. Similar to our 0% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0% Notes. The note hedges will expire upon maturity of the 0%
    Notes, or <span style="-sec-ix-hidden:Fact_c2c8af8268614a7d9201a587fc5822f5">April 2026</span>. The note hedges and warrants are separate transactions and are not part of the terms of our 0% Notes. The holders of the 0% Notes do not
    have any rights with respect to the note hedges and warrants.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">0.125 Percent
    Convertible Senior Notes and Call Spread</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of
    our 1% Notes to exchange $375.6
    million of our 1% Notes for $439.3
    million of our 0.125% Notes, and to issue $109.5
    million of our 0.125% Notes.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed above, in 2023, we repurchased $504.4
    million of our 0.125% Notes. As a result of the repurchase, we recognized a $13.4 million gain on the early retirement of debt, which we recorded as other income in our consolidated statement of operations for the year ended December 31, 2023. The gain on the early retirement of our debt is the difference between the amounts paid to repurchase our 0.125% Notes and the net carrying balance of the liability at the time that we completed the repurchases. We paid the remaining principal balance of our 0.125% Notes with $44.5 million of cash at
    maturity in December 2024.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In conjunction with the issuance of our </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes in 2019, we entered into a call spread transaction, which was
      comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our </span>0.125%
    Notes by increasing the effective conversion price on our 0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We increased our effective conversion price from $</span>83.28<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to $</span>123.38<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> with the same number of underlying
      shares as our </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes. The call spread cost us $</span>52.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, of which $</span>108.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million was for the note hedge purchase, offset by $</span>56.1<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we received for selling the warrants. Similar to our </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, our note hedges were subject to adjustment. Additionally, our
      note hedges were exercisable upon conversion of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The note hedges expired upon maturity of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in </span><span style="-sec-ix-hidden:Fact_b2783015cbc64323aab97584a4bd55af">December 2024</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The warrants will expire in
      March 2025. The note hedges and warrants were separate transactions and were not part of the terms of our </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The holders of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> did not have any rights with respect to the note hedges and warrants.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Other Terms of Convertible Senior Notes</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The 1.75% and 0% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash,
    shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of
    certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to 100 percent of the principal
    amount of the notes to be purchased, plus any accrued and unpaid interest. The 0.125% Notes were subject to similar terms.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our total interest expense for our outstanding senior convertible notes for the years ended December 31, 2024, 2023 and 2022 included $6.1 million, $5.9 million and $5.3 million, respectively, of
    non-cash interest expense related to the amortization of debt issuance costs for our convertible notes.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Financing Arrangements</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Operating Facilities</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2017, we purchased the building that houses our primary R&amp;D facility for $79.4 million and our manufacturing facility for $14.0 million. We
    financed the purchase of these two facilities with mortgage debt of $60.4 million in total. Our primary R&amp;D facility mortgage had an interest rate of 3.88
    percent. Our manufacturing facility mortgage has an interest rate of 4.20 percent. During the first five years of both mortgages, we were only required to make interest payments. We began making principal payments in 2022. Our manufacturing facility mortgage matures in August
    2027. We repaid our primary R&amp;D facility mortgage in 2022 in conjunction with a sale and leaseback transaction.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, we concurrently entered into two
    purchase and sale agreements with a real estate investor. In the same period, we closed the first transaction in which we sold the facilities at our headquarters in Carlsbad, California, which includes our primary R&amp;D facility, for a purchase price
    of $263.4 million. As a result, we de-recognized the related land and improvements, building and building improvements, which resulted in a net
    gain of $150.1 million that we reported in other income in our consolidated statements of operations. We used a portion of the sale proceeds to
    extinguish our outstanding mortgage debt on our primary R&amp;D facility of $51.3 million. In connection with this transaction, we leased back
    our headquarters facilities for an initial lease term of 15 years with options to extend the lease for two additional terms of five years each.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2023, we closed the second transaction and transferred legal ownership of two lots of undeveloped land adjacent to our headquarters to the real estate investor for a purchase price of $33 million. In connection with this transaction, we entered into a build-to-suit lease agreement with the same real estate investor to lease a new R&amp;D facility. The lessor will
    develop and construct a new building composed of R&amp;D and office space. We will design and construct tenant improvements to customize the facility&#8217;s interior space. We will lease the facility for an initial term of 15 years with options to extend the lease for two
    additional terms of five years each. The lease will commence once the structure of this new facility is completed.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Since the building is under construction and unavailable to lease, we are unable to complete the sale-leaseback evaluation under ASC 842,
    <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</span>. As a result, the land remains in our consolidated balance sheets and we accounted for the proceeds as a financial liability. We will
    reassess the transaction under the sale-leaseback accounting guidance when the facilities are available for lease commencement.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Debt Maturity Schedules</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2024 are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2025</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,657</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2026</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">643,157</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2027</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2028</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">580,091</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2029</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">360</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt and mortgage maturities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,253,062</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion included in other current liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(165</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Fixed and determinable interest</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(36,511</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(13,981</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,202,405</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Royalty Revenue Monetization</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our agreements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $500 million and we are eligible to receive up to $625 million in additional milestone payments. Under the terms of
    the agreement, Royalty Pharma will receive 25 percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to 45 percent of royalty payments in 2028, on up to $1.5
    billion in annual sales. In addition, Royalty Pharma will receive 25 percent of any future royalty payments on pelacarsen. Royalty Pharma&#8217;s
    royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $475 million or $550 million, depending on the timing and occurrence of FDA approval of pelacarsen.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the upfront payment of $500
    million as a liability related to the sale of future royalties, net of transaction costs of $10.4 million, which we are amortizing over the
    estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty
    Pharma as a reduction of the liability.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We determine the effective interest rate used to record
      interest expense under this agreement based on an estimate of future royalty payments to Royalty Pharma. As of </span>December 31, 2024 and
    2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the estimated effective interest rate under the agreement
      was </span>13.5 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our liability related to
      sale of future royalties for the year ended </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands):</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of future royalties in January 2023</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">500,000</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance costs related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,434</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty payments to Royalty Pharma</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(44,628</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68,238</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">560</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of December 31, 2023</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">513,736</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty payments to Royalty Pharma</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(44,981</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,846</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">611</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of December 31, 2024</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">542,212</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty
    payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the commercial sales of SPINRAZA, the regulatory approval and commercial sales of
    pelacarsen, competing products or other significant events.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeasesTextBlock', window );">Long-Term Obligations and Commitments</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Operating Leases</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Carlsbad Leases</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing
    facility. We lease this space under a non-cancelable operating lease. In 2020, we exercised our option to extend our lease, extending our lease term from June 2021 to August 2026. We have one remaining option to extend the lease for an additional five-year
    period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also lease an additional office space and warehouse space in Carlsbad. We lease these spaces under non-cancelable operating leases. In
    2022, we exercised our option to extend the office space lease, extending our term from January 2023 to May 2027. We have no remaining options
    to extend this lease. Our warehouse space lease in Carlsbad has an initial term ending in 2028 with no options to extend the lease.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed above in the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Financing Arrangements</span>, we lease our headquarters, which includes our primary R&amp;D facility, as part of a sale and leaseback transaction that closed in 2022. The initial lease term for our headquarters facilities is 15 years with options to extend the lease for two
    additional terms of five years each. We determined at lease inception that it was not reasonably certain that we would exercise any of the
    options to extend the lease. We expect our lease payments over the initial term to total approximately $280 million. In connection with the
    transfer of legal ownership of the two lots of undeveloped land to the real estate investor, we entered into a build-to-suit lease agreement
    with the same real estate investor who will build a new R&amp;D facility for us on those lots. The lease will commence once the structure of this new facility is completed.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Oceanside Lease</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility to be constructed by
    the lessor in Oceanside, California. We capitalized costs that we incurred related to the design and development of tenant improvements as construction-in-progress in our consolidated balance sheets. In 2023, we reached a mutual agreement with the
    lessor to terminate the lease agreement. As a result, we recorded a charge of $20 million, primarily associated with the impairment of
    construction-in-progress assets, within <span style="-sec-ix-hidden:Fact_ebdf1ed5cf6845079198439e7c520f42">SG&amp;A expense</span> in our consolidated statements of operations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Boston Leases</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We entered into an operating lease agreement for office space located in Boston, Massachusetts which commenced in August 2018. We are
    leasing this space under a non-cancelable operating lease with an initial term ending after 123 months and an option to extend the lease for an
    additional five-year term. Under the lease agreement, we received a three-month free rent period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commencement date was in
    January 2022 when the office space was ready for our tenant&#8217;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending 83 months following the sublease commencement date with no option to extend the sublease. Under the sublease
    agreement we provided a seven-month free rent period, which commenced in January 2022. We will receive lease payments over the sublease term
    totaling $9.6 million.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We entered into an operating lease agreement for another office space located in Boston, Massachusetts which commenced in 2021. We are
    leasing this space under a non-cancelable operating lease with an initial term ending 91 months following the lease commencement date and an
    option to extend the lease for <span style="-sec-ix-hidden:Fact_ddceec580074417fbe536c7c2d5d252c">an</span> additional five-year
    term. Under the lease agreement, we received a seven-month free rent period, which commenced in November 2021. Our lease payments over the
    initial term total $6.8 million.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases, we did not include
    the extension options for these leases in the original lease term because it was not reasonably certain we would exercise those extension options.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At December 31, 2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use operating lease assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">161.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">170.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average remaining lease term</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.1 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average discount rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024,
    2023, and 2022 we paid $20.5 million, $20.1 million and $4.0 million of lease payments, which were included in operating activities in our consolidated statements of cash flows.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024,
    the future payments for our operating lease liabilities are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</span> <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</span></div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Year ending December 31,</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,870</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2026</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,032</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2027</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,054</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2028</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,973</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2029</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,687</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">157,622</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total minimum lease payments</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">260,238</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: left; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Imputed interest</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(89,369</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion (included in <span style="-sec-ix-hidden:Fact_9874929ec96442469df0f0fc39baed32">other current liabilities</span>)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,064</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">161,805</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="display:none;"><br/></div>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Rent expense was $23.2 million,
    $23.1 million and $8.3 million for the
    years ended December 31, 2024, 2023
    and 2022, respectively. </div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for information about short-term and long-term debt arrangements, which includes amounts of borrowings under each line of credit, note payable, commercial paper issue, bonds indenture, debenture issue, own-share lending arrangements and any other contractual agreement to repay funds, and about the underlying arrangements, rationale for a classification as long-term, including repayment terms, interest rates, collateral provided, restrictions on use of assets and activities, whether or not in compliance with debt covenants, and other matters important to users of the financial statements, such as the effects of refinancing and noncompliance with debt covenants.</p></div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931524592">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityNoteAbstract', window );"><strong>Stockholders' Equity [Abstract]</strong></a></td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityNoteDisclosureTextBlock', window );">Stockholders' Equity</a></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">8. Stockholders</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> Equity</span></div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Preferred Stock</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are authorized to issue up to 15
    million shares of &#8220;blank check&#8221; Preferred Stock. As of December 31, 2024, there were no shares of Preferred Stock outstanding. We have designated Series C Junior Participating Preferred Stock but have no issued or outstanding shares as of December 31, 2024.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Common Stock</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2024 and 2023, we had 300 million shares of common
    stock authorized, of which 157.9 million and 144.3 million were issued and outstanding, respectively. As of December 31, 2024, total common shares
    reserved for future issuance were 48.0 million.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024,
    2023 and 2022, we issued 2.1 million, 2.3 million and 1.2 million shares of common stock, respectively, for stock option exercises, vesting of restricted stock units, and ESPP purchases. We received net
    proceeds from these transactions of $33.6 million, $49.4
    million and $6.4 million in 2024, 2023 and 2022, respectively.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2024, we completed the sale of 11.5
    million shares of our common stock through a public offering at a price of $43.50 per share. We received net proceeds of $489.1 million from the sale of these shares net of underwriting discounts and commissions and other offering expenses of $11.2 million.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock Plans</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1989 Stock Option Plan</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 1989, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that, as amended, provides for
    the issuance of non-qualified and incentive stock options for the purchase of up to 20.0 million shares of common stock to our employees,
    directors, and consultants. The plan expired in January 2024. The 1989 Stock Option Plan, or 1989 Plan, did not allow us to grant stock bonuses or restricted stock awards and prohibited us from repricing any options outstanding under the plan unless
    our stockholders approved the repricing. Options vested over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant
    and the balance vested ratably, on a monthly basis, thereafter and had a term of seven years. At December 31, 2024, no options were outstanding and no shares were available for future grant under the 1989 Plan.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2011 Equity Incentive Plan</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the issuance of
    stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to our employees, directors, and consultants. In June 2015, May 2017 and June 2019, after receiving approval from our
    stockholders, we amended our 2011 Equity Incentive Plan, or<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 2011 Plan,</span> to increase the total number of shares reserved for issuance. We increased the shares available
    under our 2011 Equity Incentive Plan from 5.5 million to 11.0 million in June 2015, from 11.0 million to 16.0 million in May 2017 and from 16.0 million to 23.0 million in June 2019. In June 2021, after receiving approval from our stockholders, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2011 Plan. The amendment increased the total number of shares of common stock authorized for issuance under the 2011 Plan from </span>23.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span>29.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and added a fungible share counting ratio whereby the share reserve will be reduced by </span>1.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> shares for each share of common stock issued pursuant to a full value award (i.e., RSU or PRSU) and
      increased by </span>1.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> shares for each share of common stock
      returning from a full value award. </span>In June 2023, after receiving approval from our stockholders, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2011 Plan to increase the total number of shares of
      common stock authorized for issuance under the 2011 Plan from </span>29.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span>35.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. </span>In June 2024,
    after receiving approval from our stockholders, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2011 Plan to increase the total number of shares of common stock authorized for issuance under the 2011 Plan
      from </span>35.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span>38.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The plan expires in June 2031. The 2011 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock
    appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our
    stockholders approve such action. Currently we anticipate awarding only stock options, RSU and PRSU awards to our employees, directors and consultants. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. Options granted after December 31, 2021 have a term of ten years.
    We have granted restricted stock unit awards to our employees under the 2011 Plan which vest annually over a four-year period. At December 31, 2024, a total of 13.3 million
    options were outstanding, of which 9.0 million were exercisable, 3.9 million restricted stock unit awards were outstanding, and 7.3 million shares were available for future grant
    under the 2011 Plan.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the 2011 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur. In addition, we implemented a change of control and severance benefit plan that provides for change of control and severance benefits to our executive officers, including our
    chief executive officer and chief financial officer, and vice presidents. If one of our executive officers or vice presidents is terminated or
    resigns for good reason during the period that begins three months before and ends twelve months following a change in control of the company, the impacted employee&#8217;s stock options and RSUs vesting will accelerate for options and RSUs outstanding as of the
    termination date.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2020 Equity Incentive Plan</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In connection with the Akcea Merger in 2020, we assumed the
      unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or
      2020 Plan. The 2020 Plan provided for the issuance of up to </span>2.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million shares of our Common Stock to our employees, directors and consultants who were employees of Akcea prior to the Akcea Merger. In the second quarter of 2021, our Compensation Committee approved an amendment to the 2020 Plan. The
      amendment decreased the total number of shares of common stock authorized for issuance under the 2020 Plan from approximately </span>2.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span>1.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. We assumed the 2020 Plan in connection with Ionis&#8217; reacquisition of all of the outstanding shares of Akcea Therapeutics, Inc. as part of the Akcea Merger.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The plan expires in December 2025. The 2020 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock
    appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our
    stockholders approve such action. Currently we anticipate awarding only stock options and RSU awards to our eligible employees, directors and consultants. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. Options granted after December 31, 2021 have a term of ten years.
    We have granted restricted stock unit awards to our employees under the 2020 Plan which vest annually over a four-year period. At December 31, 2024, a total of 0.5 million
    options were outstanding, of which 0.2 million were exercisable, 0.2 million restricted stock unit awards were outstanding, and 0.8 million shares were available for future grant
    under the 2020 Plan.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the 2020 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Corporate Transactions and Change in Control under 2011 and 2020 Plans</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the event of certain significant corporate transactions, our Board of Directors has the discretion to take one or more of the following
    actions with respect to outstanding stock awards under the 2011 and 2020 Plans:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for assumption, continuation, or substitution of a stock award by a surviving or acquiring entity (or its parent company);</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the assignment of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award to the surviving or
            acquiring corporation (or its parent company);</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">accelerate the vesting and exercisability of a stock award followed by the termination of the stock award;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the lapse of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cancel or arrange for the cancellation of a stock award, to the extent not vested or not exercised prior to the effective date of the corporate transaction, in exchange
            for cash consideration, if any, as the Board, in its sole discretion, may consider appropriate; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the surrender of a stock award in exchange for a payment equal to the excess of (a) the value of the property the holder of the stock award would have
            received upon the exercise of the stock award, over (b) any exercise price payable by such holder in connection with such exercise.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2002 Non-Employee Directors&#8217; Stock Option Plan</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2001, our Board of Directors adopted, and the stockholders subsequently approved, an amendment and restatement of the 1992 Non-Employee
    Directors&#8217; Stock Option Plan, which provides for the issuance of non-qualified stock options and restricted stock units to our non-employee directors. The name of the resulting plan is the 2002 Non-Employee Directors&#8217; Stock Option Plan, or the 2002
    Plan. In 2015, after receiving approval from our stockholders, we amended our 2002 Plan to increase the total number of shares reserved for issuance from 1.2
    million to 2.0 million. In 2020, after receiving approval from our stockholders, we further amended our 2002 Plan. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The amendments included:</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">An increase to the total number of shares reserved for issuance under the plan from </span>2.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span>2.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million shares;</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A reduction to the amount of the automatic awards under the plan;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A revision to the vesting schedule of new awards granted; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An extension of the term of the plan.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Options under this plan expire 10 years
    from the date of grant. At December 31, 2024, a total of 0.9 million options were outstanding, of which 0.8 million were exercisable, 52,000 restricted stock unit awards were outstanding, and 0.4 million
    shares were available for future grant under the 2002 Plan.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Purchase Plan</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2009, our Board of Directors adopted, and the stockholders subsequently approved, the amendment and restatement of the ESPP and we
    reserved an additional 150,000 shares of common stock for issuance thereunder. In each of the subsequent years until 2019, we reserved an
    additional 150,000 shares of common stock for the ESPP resulting in a total of 3.2 million shares authorized under the plan as of December 31, 2024.
    The ESPP permits full-time employees to purchase common stock through payroll deductions (which cannot exceed 10 percent of each employee&#8217;s
    compensation) at the lower of 85 percent of fair market value at the beginning of the purchase period or the end of each purchase period. Under
    the amended and restated ESPP, employees must hold the stock they purchase for a minimum of six months from the date of purchase. During 2024, employees purchased and we issued to employees 0.1
    million shares under the ESPP at a weighted average price of $35.93 per share. At December 31, 2024, there were 0.3 million shares available for
    purchase under the ESPP.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock Option Activity</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the stock option activity under our stock plans for the year ended December 31, 2024 (in thousands, except per share and contractual life data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Exercise</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Price Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Remaining</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contractual Term</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Years)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Aggregate</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intrinsic</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Outstanding at December 31, 2023</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,091</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.43</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,729</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49.77</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exercised</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(399</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39.55</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited/expired</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,704</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.40</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Outstanding at December 31, 2024</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,717</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.23</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.27</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,692</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Exercisable at December 31, 2024</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,089</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49.85</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.66</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,460</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The weighted-average estimated fair values of options granted were $24.37, $19.72 and $18.66 for the years ended December 31, 2024, 2023 and 2022, respectively. The total
    intrinsic value of options exercised during the years ended December 31, 2024, 2023 and 2022 were $3.6 million, $6.0 million and $1.4 million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $15.8 million, $65.1 million and $3.6 million for the years ended December 31, 2024, 2023 and 2022, respectively. For the year
    ended December 31, 2024, the weighted-average fair value of options exercised was $48.59. As of December 31, 2024, total unrecognized compensation cost
    related to non-vested stock options was $43.7 million. We expect to recognize this cost over a weighted average period of 1.1 years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Restricted Stock Unit Activity</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the RSU activity for the year ended December 31, 2024 (in thousands, except per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Grant Date Fair</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2023</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,239</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43.40</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,005</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.92</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,185</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.88</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(228</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.83</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2024</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,831</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.06</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024,
    2023 and 2022, the
    weighted-average grant date fair value of RSUs granted was $50.92, $40.51 and $36.14 per RSU, respectively. As of December 31, 2024, total unrecognized compensation cost related to RSUs was $72.6 million. We expect to recognize this cost over a weighted average period of 1.3 years. We will adjust the
    total unrecognized compensation cost for future changes in estimated forfeitures.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Performance Restricted Stock Unit Activity</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the PRSU activity for the year ended December 31, 2024 (in thousands, except per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Grant Date Fair</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2023</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">226</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.04</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">179</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">78.41</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(73</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.35</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(25</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68.21</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2024</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">307</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66.72</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024,
    2023 and 2022, the
    weighted-average grant date fair value of PRSUs granted was $78.41, $57.43 and $42.28 per PRSU, respectively. As of December 31, 2024, total unrecognized compensation cost related to PRSUs was $10.4 million. We expect to recognize this cost over a weighted average period of 1.4 years. We will adjust the
    total unrecognized compensation cost for future changes in estimated forfeitures.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-based Compensation Expense and Valuation Information</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the years ended December 31, 2024, 2023 and 2022 (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">767</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">499</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">533</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">92,403</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,826</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">73,704</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37,030</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,484</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,027</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense, net of amounts capitalized</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130,200</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105,809</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100,264</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Capitalized stock-based compensation expense</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">799</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stock-based compensation expense</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130,999</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105,809</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100,264</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense increased in 2024 compared to 2023 due to increased headcount and a higher stock price on the grant date
    of annual equity awards in 2024 compared to 2023. Refer to Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span>, for further details on how we
    determine the fair value of stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024,
    2023 and 2022, we used the
    following weighted-average assumptions in our Black-Scholes calculations:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Options:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.3 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.3 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.3 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Board of Director Stock Options:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.5 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.7 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.4 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">ESPP:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk-Free Interest Rate.</span> We base
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<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Dividend Yield.</span> We base the
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<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Volatility.</span> We use an average of
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<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Expected Life. </span>The expected term
    of stock options we have granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options we have granted based on actual and projected exercise patterns. In 2021, our Compensation
    Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options granted under these plans from <span style="-sec-ix-hidden:Fact_bd3d24dad695460d8e7018466f08295c"><span style="-sec-ix-hidden:Fact_a0ee4419d26449d89aee22da843bd7ad">seven</span></span> to ten years for stock options granted on January 1, 2022
    and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other
    means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the years ended December 31, 2024, 2023 and 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical
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<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Forfeitures.</span> We reduce stock-based
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367927087888">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxDisclosureAbstract', window );"><strong>Income Taxes [Abstract]</strong></a></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">9. Income Taxes</div>

<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss before income taxes is comprised of (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(460,712</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(334,707</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(258,493</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">644</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">742</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">508</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss before income taxes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(460,068</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(333,965</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(257,985</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our income tax expense (benefit) was as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Federal</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,492</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35,861</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,522</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(848</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,687</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,129</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">169</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">147</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current income tax expense (benefit)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,171</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,321</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total income tax expense (benefit)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,321</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to loss before income taxes. The sources
    and tax effects of the differences are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="22" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pre-tax loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(460,068</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(333,965</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(257,985</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Statutory rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(96,614</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(70,133</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State income tax net of federal benefit</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(22</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(49</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net change in valuation allowance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">152,590</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(33.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">175,388</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(52.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,951</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(40.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax credits</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(53,497</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(67,131</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(39,729</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax rate change</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,815</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2.4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,091</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-deductible compensation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,895</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(21,071</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,493</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.2</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,732</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2.3</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19,546</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,030</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5.4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">665</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(401</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">344</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,171</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,321</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9.7</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred income taxes reflect the net tax effects of temporary differences between the carrying amounts of assets and liabilities for
    financial reporting purposes and the amounts used for income tax purposes.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Significant components of our deferred tax assets and liabilities as of December 31, 2024 and 2023 are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred Tax Assets:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95,851</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,964</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax credits</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">310,703</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">239,962</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,063</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,683</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82,660</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,468</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intangible and capital assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">93,541</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,380</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,310</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,849</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Capitalized research and development expenses</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">323,560</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">238,738</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,481</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43,718</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">148,918</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">144,608</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,343</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total deferred tax assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,174,111</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,025,713</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred Tax Liabilities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Fixed assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,719</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,166</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(36,788</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(42,007</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,896</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,910</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net deferred tax asset</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,129,708</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">977,630</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Valuation allowance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,129,708</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(977,630</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total net deferred tax assets and liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024, we maintained a full valuation allowance on our net deferred tax assets. We determined the valuation allowance in
    accordance with the provisions of ASC 740, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Accounting for Income Taxes</span>, which requires an assessment of both positive and negative evidence when
    determining whether it is more likely than not that deferred tax assets are realizable. Our recent history of cumulative losses and expected near-term future losses require us to record a full valuation allowance against all net deferred tax assets. We
    will maintain a full valuation allowance on net deferred tax assets until sufficient positive evidence exists to support reversal of the valuation allowance<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our valuation allowance increased by $152
    million from December 31, 2023 to December 31, 2024.
    The increase was primarily related to increases in our deferred tax assets for capitalized research and development expenses and tax credits.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2024, we had
    federal and state, primarily California, tax net operating loss carryforwards of $290.2 million and $526.9 million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2032. At December 31, 2024, we also had federal and California research and development tax credit carryforwards of $234.2 million and $137.6 million, respectively. Our federal research and
    development tax credit carryforwards will begin to expire in 2037. Our California research and development tax credit carryforwards are available indefinitely.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Utilization of the net operating loss and tax credit carryforwards may be subject to an annual limitation due to the ownership change
    limitations provided by the Internal Revenue Code of 1986, as amended, and similar state provisions. The annual limitation may result in the expiration of net operating losses and credits before utilization.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We analyze filing positions in all U.S. federal, state and foreign jurisdictions where we file income tax returns, and all open tax years
    in these jurisdictions to determine if we have any uncertain tax positions on any of our income tax returns. We recognize the impact of an uncertain tax position on an income tax return at the largest amount that the relevant taxing authority is
    more-likely-than not to sustain upon audit. We do not recognize uncertain income tax positions if they have less than 50 percent likelihood of the applicable tax authority sustaining our position.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our gross unrecognized tax benefits <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(in thousands):</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance of unrecognized tax benefits</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43,298</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56,567</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55,085</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Decrease for lapse of statute of limitations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,579</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14,993</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Decrease for prior period tax positions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(110</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(267</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for prior period tax positions</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">429</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">259</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,650</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,032</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,490</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance of unrecognized tax benefits</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,161</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43,298</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56,567</div>
        </td>

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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in the balance of unrecognized tax benefits at December 31, 2024, 2023 and 2022 was $0.3 million, $0.3 million and $6.2 million respectively, that if we recognized, could
    impact our effective tax rate, subject to our remaining valuation allowance.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any material changes to our gross unrecognized tax benefits within the next 12 months.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize interest and/or penalties related to income tax matters in income tax expense. During the years ended December 31, 2024, 2023 and 2022, we recognized $0.1 million, $0.1 million and $0.8 million, respectively, of
    accrued interest and penalties related to gross unrecognized tax benefits.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are subject to taxation in the U.S. and various state and
      foreign jurisdictions. U.S. tax years 2021 through 2023 remain open to examination and tax years 2020 through 2023 remain open to examination by major state taxing jurisdictions, primarily California, although net operating loss and credit
      carryforwards generated prior to these periods may still be adjusted upon examination by the Internal Revenue Service or state tax authorities if they have been used in an open period or are used in a future period</span>.</div>
<span></span>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Employment Benefits<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">10. Employment Benefits</div>

<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have employee 401(k) salary deferral plans covering all employees. Employees could make contributions by withholding a percentage of
    their salary up to the IRS annual limits of $23,000 and $30,500 in 2024 for employees under 50 years old and employees 50 years old or over, respectively. We made
    approximately $8.6 million, $7.1
    million and $5.6 million in matching contributions for the years ended December 31, 2024, 2023 and 2022, respectively.</div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for retirement benefits.</p></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367930917792">
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We operate as a <span style="-sec-ix-hidden:Fact_2519ca12728c45f9b7af0ac92fa19388">single</span>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">109,016</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(40,205</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consolidated net loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(453,897</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(366,286</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(269,722</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for reporting segments including data and tables. Reportable segments include those that meet any of the following quantitative thresholds a) it's reported revenue, including sales to external customers and intersegment sales or transfers is 10 percent or more of the combined revenue, internal and external, of all operating segments b) the absolute amount of its reported profit or loss is 10 percent or more of the greater, in absolute amount of 1) the combined reported profit of all operating segments that did not report a loss or 2) the combined reported loss of all operating segments that did report a loss c) its assets are 10 percent or more of the combined assets of all operating segments.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 48<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-48<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> 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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931563776">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fourth Quarter Financial Data (Unaudited)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">13. Fourth Quarter Financial Data (Unaudited)</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following financial information reflects all normal recurring adjustments, which are, in the opinion of management, necessary for a
    fair statement of the results of the interim periods. Summarized fourth quarter data for 2024 and 2023 are as follows (in thousands, except per share data).</div>

<div><br/>
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  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31,</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">226,577</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">324,505</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">337,398</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">330,627</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss from operations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(110,821</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,122</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(104,349</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share (3) (4)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.66</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.06</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Diluted net loss per share (3) (5)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.66</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.06</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue was lower in the three months ended December 31, 2024 compared to the same period in 2023 primarily due to significant partner payments earned in the fourth quarter of 2023, including the $</span>50<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment we earned from AstraZeneca when the FDA
              approved WAINUA for ATTRv-PN in the U.S., $</span>36<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
              million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis. </span>In addition, WAINUA
            joint development revenue decreased in the three months ended December 31, 2024 compared to the same period in 2023 as development activities relating to ATTRv-PN wound down with the launch of WAINUA.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses were relatively consistent in the three months
            ended December 31, 2024 compared to the same period in 2023.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </span>compute net loss per share independently for each quarter during <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</span></div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies, </span>we compute basic net loss per share by dividing the total net loss by our weighted-average number of common shares outstanding
            during the period.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incurred a net loss for the fourth quarter of 2024 and 2023. As a
            result, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive.</div>
        </td>

  </tr>


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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367927463088">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Cybersecurity Risk Management and Strategy Disclosure<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_cyd_CybersecurityRiskManagementStrategyAndGovernanceAbstract', window );"><strong>Cybersecurity Risk Management, Strategy, and Governance [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_cyd_CybersecurityRiskManagementProcessesForAssessingIdentifyingAndManagingThreatsTextBlock', window );">Cybersecurity Risk Management Processes for Assessing, Identifying, and Managing Threats [Text Block]</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risk management and strategy</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have implemented and maintain various information security processes designed to detect, respond to, recover, and protect our
    technology ecosystem from cybersecurity threats. These processes are designed to identify, assess, and manage material risks that may result from cybersecurity threats and apply to our critical technologies inclusive of networks, third party hosted
    services, communications systems, hardware, software, and critical data, including intellectual property and confidential information that is proprietary, strategic, or competitive in nature.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our Information Technology department, led by our Senior Vice President, Information Technology, helps to detect, respond to, and manage
    cybersecurity threats and risks by monitoring and evaluating our threat environment using various manual and automated tools in certain environments and systems and other methods including, for example:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">analyzing reports of certain threats and actors;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">conducting scans of the threat environment;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">evaluating our and our industry&#8217;s risk profile;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">evaluating certain threats reported to us;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">conducting internal and external audits;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">conducting threat assessments for certain internal and external threats; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">conducting vulnerability assessments designed to identify vulnerabilities.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Depending on the environment, system and data, we have implemented and maintain various technical, physical, and organizational measures,
    processes, standards, and policies designed to manage and mitigate material risks from cybersecurity threats to our critical technologies and data, including, for example:</div>

<div><br/>
  </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">incident response plan;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">disaster recovery/business continuity plans;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">risk assessments;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">encryption of certain data;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">network security and access controls for certain systems;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">physical security;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">asset management, tracking and disposal;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">systems monitoring; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">employee training.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our assessment and management of material risks from cybersecurity threats are integrated into the Company&#8217;s overall risk management processes. For example, cybersecurity risk is assessed as a component of our enterprise risk
    management program. In addition, we have developed a process whereby our senior management evaluates material risks from cybersecurity threats against our overall business objectives and reports certain cybersecurity incidents to the Audit Committee of
    the Board of Directors, which evaluates our overall enterprise risk. </div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use third-party providers to perform various functions throughout our business, such as application providers and hosting companies. We use third-party providers to assist us from time to time in an effort to identify, assess, and manage material risks from cybersecurity threats, including, for example, legal counsel, cybersecurity consultants, cybersecurity software providers, penetration testing firms, and forensic investigators.&#160;The Company maintains a risk-based approach and process designed to identify and oversee cybersecurity risks presented by third parties, including vendors, service providers and other external users of the Company&#8217;s systems, as well as the systems of third parties that could materially impact our business if there is a cybersecurity incident affecting those third-party systems.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For an additional description of the risks from cybersecurity
    threats that may materially affect us and how they may do so, see our risk factors under Item 1A, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk Factors</span>, in this Annual Report on Form 10-K, including the risk factor titled &#8220;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">We are
      dependent on data as well as information technology systems and infrastructure, which exposes us to data protection risks</span>.&#8221;</div>
<span></span>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our assessment and management of material risks from cybersecurity threats are integrated into the Company&#8217;s overall risk management processes. For example, cybersecurity risk is assessed as a component of our enterprise risk
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    the Board of Directors, which evaluates our overall enterprise risk. </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For an additional description of the risks from cybersecurity
    threats that may materially affect us and how they may do so, see our risk factors under Item 1A, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk Factors</span>, in this Annual Report on Form 10-K, including the risk factor titled &#8220;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">We are
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our Board of Directors addresses our cybersecurity risk management as part of its general oversight function. <span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">The Audit Committee of the Board of Directors is responsible for overseeing our cybersecurity risk management processes, including oversight and mitigation of risks from cybersecurity threats.</span> The Audit Committee also oversees our internal audit department and management&#8217;s internal controls over financial reporting, including with respect to cybersecurity.</div>

<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cybersecurity risk assessment and management processes are implemented and maintained by our Senior Vice President, Information Technology, <span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">who holds an undergraduate
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our Senior Vice President, Information Technology is
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Section 106<br> -Subsection b<br> -Paragraph 1<br> -Subparagraph ii<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Section 16K<br> -Subsection b<br> -Paragraph 1<br> -Subparagraph ii<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Section 106<br> -Subsection b<br> -Paragraph 2<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Section 16K<br> -Subsection b<br> -Paragraph 2<br></p></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the quarter ended December 31, 2024, our
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 1<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph B<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph C<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph C<br></p></div>
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<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph A<br></p></div>
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<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph A<br></p></div>
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<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph D<br></p></div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367926506736">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies (Policies)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Organization and Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConsolidationPolicyTextBlock', window );">Basis of Presentation</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis of Presentation</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;).</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SegmentReportingPolicyPolicyTextBlock', window );">Segment Information</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We operate as a <span style="-sec-ix-hidden:Fact_0a919095f48f42f79abafacb21f6d831">single</span> segment, Ionis
    operations, because our chief operating decision maker, or CODM, reviews operating results on an aggregate basis and manages our operations as a single operating segment. Refer to Note 12, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Information</span>, for further details on our segment information.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UseOfEstimates', window );">Use of Estimates</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Use of Estimates</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the United States, or
    U.S., that require us to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerPolicyTextBlock', window );">Revenue Recognition</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue Recognition</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting
    receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include
    the amounts within deferred revenue in our consolidated balance sheets.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities
    performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC,
    Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration
      arrangements within the scope of ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that contain multiple elements, we </span>first<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
      determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC </span>606<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. When we determine elements of a collaboration do not
      reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with
    multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our WAINUA collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue; while
    we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as selling, general and administrative, or SG&amp;A, expense and research and development, or R&amp;D, expense,
    respectively.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of
    revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Identify the contract</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner or customer.</div>

<div><br/>
  </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">2.</span></td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Identify the performance obligations</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the
    contract.</div>

<div><br/>
  </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">3.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Determine the transaction price</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration
      agreement, including any variable consideration.</div>

<div><br/>
    </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">4.</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Allocate the transaction price</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Next, we allocate the transaction price to each of our
        performance obligations. When we have to allocate the transaction price to more than </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligation, we make estimates of the relative stand-alone
        selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do
        not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</span></div>

<div><br/>
  </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">5.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Recognize revenue</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize revenue in </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ways, over time or at a point in time. We recognize revenue over time when we are executing on our
        performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a
        specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</span></div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue, which
      in certain cases may require us to estimate our royalty revenue.</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Amendments to Agreements</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the
    accounting for the amendment:</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the goods and/or services are sold at a stand-alone selling price.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at
      a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are
      distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment
      to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a
      cumulative-effect adjustment.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Multiple agreements</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to
    determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div>

<div><br/>
  </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the agreements were negotiated together with a single objective;</div>
        </td>

  </tr>


</table>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div>
        </td>

  </tr>


</table>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting
    guidance requires us to account for them as a combined arrangement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative
      Arrangements and Licensing Agreements</span>, for further discussion of our 2018 neurology collaboration with Biogen that included multiple agreements which we negotiated concurrently and in contemplation of one another.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ReceivablesPolicyTextBlock', window );">Contracts Receivable</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we
      have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts
      receivable to be unconditional. We typically receive payment within </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;quarter of billing our partner or customer</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024,
    approximately 95.6 percent of our contracts receivables were from three significant customers. As of December 31, 2023, approximately 87.8 percent of our contracts receivables were from one
    significant customer.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy', window );">Unbilled Royalties</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled Royalties</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our unbilled royalties represent our right to receive consideration from our partners in advance of when we are eligible to bill them for
    royalties. We include these unbilled amounts in other current assets in our consolidated balance sheets.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueRecognitionPolicyTextBlock', window );">Deferred Revenue</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive
      payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue in our consolidated balance sheets.</span> During the years ended December 31, 2024 and 2023, we recognized $166.1 million and $78.2 million of revenue from
    amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostOfSalesPolicyTextBlock', window );">Cost of Sales</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Sales</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs
    and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpensePolicy', window );">Research, Development and Patent Expenses</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Patent Expenses</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and
    manufacturing costs, patents and other expenses that are directly related to our R&amp;D operations. We expense R&amp;D costs as we incur them. When we make payments for R&amp;D services prior to the services being rendered, we record those amounts as
    prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in R&amp;D expenses are costs associated with our partner agreements. In 2024, 2023 and 2022, patent expenses were $5.3 million, $4.3 million and $4.7 million, respectively.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxPolicyTextBlock', window );">Income Taxes</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities
    for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development
    credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and
    measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight
    of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit
    as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes.
    Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these
    reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the
    provision for income taxes in the period in which we make such determination.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In
    assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We
    base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from
    our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be
    realized. </div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerSharePolicyTextBlock', window );">Basic and Diluted Net Loss Per Share</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss per Share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We compute basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the
    period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Diluted net loss per share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024,
    2023 and 2022, we incurred a net
    loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss
    per share:</div>

<div><br/>
  </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span>0%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span>0%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Stock Purchase Plan, or ESPP.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2024 and 2023, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, would also
    have had an anti-dilutive effect on net loss per share.</div>

<div><br/>
  </div>
<span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">As of December 31, 2024, 2023 and 2022, we had outstanding warrants related to our 0% Notes and 0.125% Notes. We will include the shares issuable
    under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</span><span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy', window );">Stock-Based Compensation Expense</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-Based Compensation Expense</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock
    purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service
    period in our consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated
    multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award
    were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Stock Options and Stock Purchase Rights:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant
    date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the
    awards, and actual and projected employee stock option exercise behaviors. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted
    based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options
    granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this
    change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the years ended December 31, 2024, 2023 and 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we
    gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RSU&#8217;s:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest
    annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. The annual RSUs we granted to our board of directors after June 2020 fully vest after one year. The RSUs we granted to board members at their initial appointment to the board of directors vest annually over a three-year period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PRSU&#8217;s:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added
    PRSU awards to the compensation for our other Section 16 officers. Under the terms of the PRSUs we granted in 2020 through 2022, <span style="-sec-ix-hidden:Fact_65d15117ab79462e81dfb8bbb86a0107"><span style="-sec-ix-hidden:Fact_e9934b85c6af480197be8d0d8b5ea434"><span style="-sec-ix-hidden:Fact_5599af32346c4fce91fa6d27caf4b474">one third</span></span></span>
    of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period
    commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant
    and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third
    anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 150 percent of the target number
    depending on our relative TSR. These PRSU awards also included an alternative three-year payout mechanism, or the Alternative Calculation, under
    which we must calculate an alternative payout at the end of the final three-year measurement period assuming the only measurement period for all
    shares under the award was the three-year period. If the Alternative Calculation is greater than payouts under the sum of the three years, then such PRSU award will pay out to achieve the number of shares payable under the Alternative Calculation.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the PRSUs we granted in 2024 and 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period based on our relative TSR as
    compared to a peer group of companies and as measured at the end of the performance period. Under the terms of the grants, no number of PRSUs is
    guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 200 percent of the target number depending on our relative TSR.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which
    represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Note 8, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Stockholders&#8217; Equity,</span>
    for additional information regarding our stock-based compensation plans.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskCreditRisk', window );">Concentration of Credit Risk</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Concentration of Credit Risk</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term
    investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions,
    corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#8217;s, Standard &amp; Poor&#8217;s, or S&amp;P, or Fitch, respectively. We have established guidelines relative to
    diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueOfFinancialInstrumentsPolicy', window );">Fair Value Measurements</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value Measurements</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and
    accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1,
    defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly
    traded biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale
    securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments
    from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value
    to the fair value based on observable market prices.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentPolicyTextBlock', window );">Cash, Cash Equivalents and Investments</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, Cash Equivalents and Investments</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term
    investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for
    identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our consolidated statements of
    operations. We use the specific identification method to determine the cost of securities sold.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have equity investments of less than 20 percent ownership in public and private biotechnology companies that we received as part
      of a technology license or partner agreement. At December 31, 2024, we held equity investments in three publicly traded companies and seven privately held companies.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our consolidated
    statements of operations. We account for our equity investments in publicly traded companies at their listed stock price. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting
    from observable price changes in orderly transactions for the identical or similar investment of the same issuer.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryPolicyTextBlock', window );">Inventories</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventories</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory in our consolidated balance sheets at the lower of cost or net realizable value under the first-in, first-out
    method, or FIFO. Our inventory costs include material, labor and overhead costs. Our raw materials include active pharmaceutical ingredient, or API, for commercial medicines. We capitalize inventory costs related to drug products when we consider
    future commercialization to be probable and expect to realize future economic benefit. When evaluating whether to capitalize inventory costs, we consider various factors, including the likelihood of receiving required regulatory approvals,
    communications from regulatory agencies such as safety or efficacy concerns, underlying manufacturing processes and supply chain matters, shelf life of the inventory, market trends such as competition and pricing, potential legal matters and potential
    reimbursement strategies. We record inventory costs that do not meet our capitalization requirements as R&amp;D expense in our consolidated statements of operations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated
    net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory and historical write-offs.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CapitalizedMaterialsPolicyPolicyTextBlock', window );">Capitalized Materials</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Capitalized Materials</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We capitalize the costs of certain materials that we purchase for use in manufacturing our medicines in our clinical development programs
    because until we use these materials, they have alternative future uses. We can use these materials in multiple products and, as a result, each material has future economic value independent of the development status of any single medicine. We include
    capitalized materials in other current assets in our consolidated balance sheets and expense these costs as R&amp;D expenses when the materials are used. We review our capitalized materials periodically for continued alternative future use and reduce
    the carrying value of items in the period in which an impairment is identified.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2024, we reclassified capitalized costs related to materials used in our clinical development programs from inventories to other
    current assets in our consolidated balance sheets. As such, we reclassified the respective prior period amounts to conform with the current year presentation.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentPolicyTextBlock', window );">Property, Plant and Equipment</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which we
    determine as the following (in years):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 80.34%; vertical-align: bottom;"> </td>

    <td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Useful Lives</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software, laboratory, manufacturing and other equipment</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3 to 10</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building, building improvements and building systems</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15 to 40</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land improvements</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leasehold improvements</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 15</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 10</div>
        </td>

  </tr>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived
    assets, which include property, plant and equipment, for impairment whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AccruedLiabilitiesPolicyPolicyTextBlock', window );">Accrued Liabilities</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. We estimate our liability
    for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to third-party clinical management
    costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted
    fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these costs may differ
    materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtPolicyTextBlock', window );">Convertible Debt</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for each of our convertible debt instruments as a
      single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt
      issuance costs as contra-liabilities in our consolidated balance sheets at issuance and amortize them over the contractual term of the convertible debt instrument using the effective interest rate. </span>The<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> balances of our convertible senior notes presented in our consolidated balance sheets represent the principal balance of each convertible debt instrument less debt issuance costs.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024, we
    had two outstanding convertible senior notes, our 1.75%
    Notes, which mature in June 2028, and our 0% Notes, which mature in April 2026. Our 0.125% Notes matured in December 2024. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and
      Commitments</span>, for further details on our convertible senior notes.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DerivativesPolicyTextBlock', window );">Call Spread</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Call Spread</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the issuance of our 0%
    Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of
    purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not
    meet the definition of a liability using the guidance contained in ASC Topic 480; therefore, we account for the note hedges and warrants using the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Derivatives







      and Hedging &#8211; Contracts in Entity&#8217;s Own Equity</span> accounting guidance contained in ASC Topic 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified
    in shareholders&#8217; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our consolidated balance sheets. We reassess our ability to continue to classify any
    outstanding note hedges and warrants in shareholders&#8217; equity at each reporting period. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for
    further details on the call spread transactions. </div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock', window );">Liability Related to Sale of Future Royalties</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Liability Related to Sale of Future Royalties</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. Under our agreement with Royalty Pharma, we record upfront payments and milestone payments we receive from the sale of future
    royalties as a liability, net of transaction costs. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for further details on the agreement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We record royalty payments made to Royalty Pharma as a reduction of the liability or accrued interest and amortize the transaction costs
    over the estimated life of the royalty stream. We account for the associated interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the
    related product and recognizes the related revenue.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense using our
    current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material
    change in our estimate, we will prospectively adjust the effective interest rate and the related interest expense.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeLeasesPolicyTextBlock', window );">Leases</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Leases</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use
    operating lease asset and associated short- and long-term operating lease liability in our consolidated balance sheets for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term
    and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we
    will pay over the lease term.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal
    options if we conclude we are reasonably certain to exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease
    term.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information
    available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease.
    Our leases do not include material variable or contingent lease payments. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock', window );">Recent Accounting Standards</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recent Accounting Standards</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2023, the Financial Accounting Standards Board, or FASB, issued Accounting Standard Update, or ASU, 2023-07, which provides
    updated guidance on segment reporting. The guidance requires public companies to disclose significant expenses that are regularly provided to the CODM, other segment items for each reportable segment and measures of segment profit or loss used by the
    CODM for allocating resources. In addition, the updated guidance requires public companies with a single reportable segment to provide all disclosures required under ASC 280, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Reporting</span>, and public companies to include in interim reports all disclosures related to a reportable segment&#8217;s profit or loss and assets that are currently required in annual reports. This update is effective for
    annual periods beginning after December 15, 2023 and interim periods beginning after December 15, 2024. The guidance is applied on a retrospective basis for all periods presented in the financial statements, unless it is impracticable. We adopted the
    annual reporting requirements in our 2024 Annual Report on Form 10-K. We expect to adopt the interim reporting requirements in our Quarterly Report on Form 10-Q in the first quarter of 2025. Refer to Note 12, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Information</span>, for further details on our segment information.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2023, the FASB issued ASU 2023-09, which provides updated guidance on income tax disclosures. The new guidance requires
    companies to provide additional disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions and
    unrecognized deferred tax liabilities. This update is effective for annual periods beginning after December 15, 2024. Early adoption of this guidance is permitted. The guidance may be applied on a prospective or retrospective basis. We currently plan
    to adopt this guidance in our 2025 Annual Report on Form 10-K.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2024, the FASB issued ASU 2024-03, which requires public companies to disclose disaggregated expenses for certain expenses in
    the income statement. This update is effective for annual periods beginning after December 15, 2026 and interim periods within annual periods beginning after December 15, 2027. Early adoption of this guidance is permitted. The guidance may be applied
    on a prospective or retrospective basis. We are currently assessing the impact and timing of adopting this update.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2024, the FASB issued ASU 2024-04 to clarify the guidance for determining whether to account for early settlements of
    convertible debt as induced conversions or extinguishments. This update is effective for annual periods beginning after December 15, 2025 and interim periods within those annual periods. Early adoption of this guidance is permitted. The guidance may be
    applied on a prospective or retrospective basis. We are currently assessing the impact and timing of adopting this update.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any other recently issued accounting standards to have a material impact to our financial statements or disclosures.</div>
<span></span>
</td>
</tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for estimating accrued liabilities, including the liability for preclinical and clinical development costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for capitalization of materials used in manufacturing medicines in clinical development programs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of inventory accounting policy for liability related to sale of future royalties.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for credit risk.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 825<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478898/942-825-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -SubTopic 10<br> -Topic 275<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy regarding (1) the principles it follows in consolidating or combining the separate financial statements, including the principles followed in determining the inclusion or exclusion of subsidiaries or other entities in the consolidated or combined financial statements and (2) its treatment of interests (for example, common stock, a partnership interest or other means of exerting influence) in other entities, for example consolidation or use of the equity or cost methods of accounting. The accounting policy may also address the accounting treatment for intercompany accounts and transactions, noncontrolling interest, and the income statement treatment in consolidation for issuances of stock by a subsidiary.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483426/235-10-50-4<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481203/810-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for cost of product sold and service rendered.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Name Accounting Standards Codification<br> -Topic 705<br> -Publisher FASB<br> -URI https://asc.fasb.org/705/tableOfContent<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy related to debt. Includes, but is not limited to, debt issuance costs, the effects of refinancings, method of amortizing debt issuance costs and original issue discount, and classifications of debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481544/470-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtPolicyTextBlock</td>
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<td><strong> Period Type:</strong></td>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DerivativesPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for its derivative instruments and hedging activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 815<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480434/815-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-9<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(n))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480434/815-10-50-1A<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480434/815-10-50-1<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480434/815-10-50-4<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480434/815-10-50-7<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DerivativesPolicyTextBlock</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for computing basic and diluted earnings or loss per share for each class of common stock and participating security. Addresses all significant policy factors, including any antidilutive items that have been excluded from the computation and takes into account stock dividends, splits and reverse splits that occur after the balance sheet date of the latest reporting period but before the issuance of the financial statements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerSharePolicyTextBlock</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FairValueOfFinancialInstrumentsPolicy">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for determining the fair value of financial instruments.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 825<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FairValueOfFinancialInstrumentsPolicy</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for income taxes, which may include its accounting policies for recognizing and measuring deferred tax assets and liabilities and related valuation allowances, recognizing investment tax credits, operating loss carryforwards, tax credit carryforwards, and other carryforwards, methodologies for determining its effective income tax rate and the characterization of interest and penalties in the financial statements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-20<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 19<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-19<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482525/740-10-45-25<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(h)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479886/946-10-S99-3<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 17<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-17<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-9<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482525/740-10-45-28<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482765/220-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of inventory accounting policy for inventory classes, including, but not limited to, basis for determining inventory amounts, methods by which amounts are added and removed from inventory classes, loss recognition on impairment of inventories, and situations in which inventories are stated above cost.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 330<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483080/330-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483489/210-10-50-1<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483426/235-10-50-4<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 912<br> -SubTopic 330<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478411/912-330-50-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 330<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org/330/tableOfContent<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 330<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483080/330-10-50-4<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 6<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 270<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482989/270-10-45-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryPolicyTextBlock</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for investment in financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(3)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(d))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479886/946-10-S99-3<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(f)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479886/946-10-S99-3<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(f)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479886/946-10-S99-3<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(f)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479886/946-10-S99-3<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 320<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 12<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477271/946-320-S99-12<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 320<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 19<br> -Subparagraph (2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477271/946-320-S99-19<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentPolicyTextBlock</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for leasing arrangement entered into by lessee.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeLeasesPolicyTextBlock</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy pertaining to new accounting pronouncements that may impact the entity's financial reporting. Includes, but is not limited to, quantification of the expected or actual impact.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for long-lived, physical asset used in normal conduct of business and not intended for resale. Includes, but is not limited to, work of art, historical treasure, and similar asset classified as collections.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 360<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482099/360-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -SubTopic 360<br> -Topic 958<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477798/958-360-50-6<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -SubTopic 360<br> -Topic 958<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477798/958-360-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for receivable. Includes, but is not limited to, accounts receivable and financing receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 310<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481962/310-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 310<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481569/310-20-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 310<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481962/310-10-50-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 310<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481962/310-10-50-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 310<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481962/310-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ReceivablesPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for costs it has incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 730<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 05<br> -Paragraph 1<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483044/730-10-05-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchAndDevelopmentExpensePolicy</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue from contract with customer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 17<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-17<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 19<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-19<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 18<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-18<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 18<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-18<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-20<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-20<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-20<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-20<br><br>Reference 9: http://www.xbrl.org/2003/role/exampleRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (e)<br> -SubTopic 10<br> -Topic 235<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483426/235-10-50-4<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Topic 606<br> -Publisher FASB<br> -URI https://asc.fasb.org/606/tableOfContent<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerPolicyTextBlock</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>dtr-types:textBlockItemType</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueRecognitionPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue. Includes revenue from contract with customer and from other sources.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-07(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483426/235-10-50-4<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (e)<br> -SubTopic 10<br> -Topic 235<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483426/235-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueRecognitionPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SegmentReportingPolicyPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for segment reporting.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 47<br> -Subparagraph (bb)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-47<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 54<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-54<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 36<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-36<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 47<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-47<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (e)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SegmentReportingPolicyPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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</tr>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for award under share-based payment arrangement. Includes, but is not limited to, methodology and assumption used in measuring cost.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(v)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.C.Q3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479830/718-10-S99-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.D.1.Q5)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479830/718-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.D.3.Q2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479830/718-10-S99-1<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.D.2.Q6)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479830/718-10-S99-1<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org/718/tableOfContent<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for treatment of receivables that are billable but have not been billed as of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(3)(c)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 310<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org/310/tableOfContent<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for the use of estimates in the preparation of financial statements in conformity with generally accepted accounting principles.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-9<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-4<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 275<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -SubTopic 10<br> -Topic 275<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 11<br> -SubTopic 10<br> -Topic 275<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-11<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -SubTopic 10<br> -Topic 275<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-12<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-8<br></p></div>
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<tr>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367930943184">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies (Tables)<br></strong></div></th>
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<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which we
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the useful lives of physical assets used in the normal conduct of business and not intended for resale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367930235856">
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<td class="text">&#160;<span></span>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

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          <div style="text-align: justify; text-indent: -19.4pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,810</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Work in process</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,679</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,477</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">276</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">154</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventories</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,512</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,441</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentTextBlock', window );">Property, Plant and Equipment</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our property, plant and equipment consisted of the following (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="background-color: #CCEEFF; vertical-align: bottom; white-space: nowrap; width: 76%;">
          <div style="text-align: left; margin-left: 6.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software, laboratory, manufacturing and other equipment</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86,540</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79,885</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building, building improvements and building systems</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,228</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,228</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leasehold improvements</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,375</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,276</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,855</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,844</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">191,998</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">159,233</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Accumulated depreciation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(106,316</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(96,759</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">85,682</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62,474</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,569</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,569</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; margin-left: 33.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">94,251</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,043</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfAccruedLiabilitiesTableTextBlock', window );">Accrued Liabilities</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our accrued liabilities consisted of the following (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">216,090</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">240,379</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">242,314</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,207</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other commercial revenue:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA revenue, net</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,189</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,913</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30,051</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,590</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,299</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30,993</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total other commercial revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56,779</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68,212</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61,044</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293,076</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">308,591</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">303,358</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development revenue:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">332,647</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">352,657</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">207,222</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA joint development revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79,415</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">126,399</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76,787</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">412,062</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">479,056</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">284,009</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: 54pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">705,138</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367932641632">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember', window );">AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
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<div><br/>
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<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with AstraZeneca</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Biogen</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">368,058</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">350,146</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">366,696</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember', window );">GSK [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with GSK (in thousands, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with GSK</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,000</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationMember', window );">Novartis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Novartis (in thousands, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Novartis</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37,762</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30,194</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">237</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less than 1%</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Roche (in thousands, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Roche</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,871</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48,838</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67,202</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_OtsukaCollaborationsMember', window );">Otsuka [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the year ended December 31, 2024, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amount):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Otsuka</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46,856</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56,480</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamPharmaceuticalsIncMember', window );">Alnylam [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2024, 2023 and 2022, we earned the following revenue from our relationship with Alnylam (in thousands, except percentage amounts):</div>

<div><br/>
    </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Alnylam</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,110</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,426</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,389</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45368017012304">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsAbstract', window );"><strong>Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock', window );">Contract Maturity of Available-for-Sale Securities</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2024:</div>

<div><br/>
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<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">One year</span>
            or less</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">one year</span>
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">two years</span>
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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  </tr>


</table>
<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock', window );">Summary of Investments</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortized</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2024</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">593,810</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">487</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(240</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">594,057</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143,647</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">287</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(39</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143,895</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">657,285</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">825</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">657,990</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,516</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,524</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,402,258</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,607</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(399</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,403,466</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">439,561</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">723</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,275</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">438,009</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,255</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(289</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,103</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">149,086</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">124</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(476</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">148,734</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">698</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">696</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">654,600</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">984</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,042</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">652,542</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,056,858</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,591</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,441</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,056,008</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,660</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Privately held equity securities included in deposits and other assets (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,115</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,001</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,093</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35,012</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,027</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(13,753</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46,286</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,091,870</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,618</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(17,194</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,102,294</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2023</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">559,967</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">157</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,625</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">557,499</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">224,711</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(611</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">224,164</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">513,784</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">152</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,889</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">512,047</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,757</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(113</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,686</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,316,219</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">415</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,238</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,311,396</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">243,151</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,270</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(692</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">243,729</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">110,138</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">547</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(21</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">110,664</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,239</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(480</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">295,632</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,466</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,469</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">651,628</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,063</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,197</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">653,494</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,967,847</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,478</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,435</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,964,890</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">236</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,832</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,301</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Privately held equity securities included in deposits and other assets (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,115</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,001</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,125</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42,991</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35,012</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,237</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,957</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49,292</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,002,859</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,715</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(17,392</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,014,182</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Includes investments classified as cash equivalents in our consolidated
            balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our publicly traded equity securities are included in other current
            assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2024, we recorded a $1.0 million net <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">unrealized loss in our consolidated statement of
              operations related to changes in the fair value of our investments in publicly traded companies.</span></div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at</span> cost minus impairments, plus or minus changes resulting from observable price changes in
            orderly transactions for the identical or similar investment of the same issuer, which are Level 3 inputs. In the year ended December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recorded a $</span>2.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million net unrealized loss in our consolidated statements of operations related to observable price changes of our investments in privately held companies.</span></div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionFairValueTableTextBlock', window );">Temporarily Impaired Investments</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our investments we considered to be temporarily impaired at&#160;</span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;(in thousands, except for number of investments):</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Temporary</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">274</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">488,949</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,463</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,713</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(52</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">516,662</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,515</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67,854</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(328</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">252,926</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(503</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,173</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(93</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">277,099</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(596</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">643</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">129</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">772</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">696</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">696</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">346</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">811,068</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,296</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52,015</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(145</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">863,083</div>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueDisclosuresAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at December 31, 2024 and 2023&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
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  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">180,445</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">180,445</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

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          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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  <tr>

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          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">208,998</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">208,998</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

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          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">806,724</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">806,724</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,524</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,524</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

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          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (2)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">696</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">696</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (3)</div>
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,241,716</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">992,432</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,249,284</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">185,424</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">185,424</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (4)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">801,228</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">801,228</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">334,828</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">334,828</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">807,679</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">807,679</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,155</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,155</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (3)</div>
          </div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,301</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,301</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,156,615</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">999,404</div>
        </td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,157,211</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

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  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in cash and cash equivalents in our consolidated balance
            sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
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  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in short-term investments in our consolidated balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in other current assets in our consolidated balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
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        </td>

  </tr>


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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931610176">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtDisclosureAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfDebtInstrumentsTextBlock', window );">Long-Term Obligations</a></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The carrying value of our long-term obligations was as follows (in thousands):</div>

<div><br/>
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<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">1.75</span>%
            convertible senior notes</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">565,026</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">562,285</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">0</span>%
            convertible senior notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">628,535</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">625,380</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">542,212</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">513,736</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">170,869</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,969</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mortgage debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,714</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,859</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other obligations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43,425</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,714</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,958,781</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,922,943</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: current portion</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,279</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(8,831</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total Long-Term Obligations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,949,502</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,914,112</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ConvertibleNotesDisclosureLineItems', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock', window );">Debt Maturity Schedules</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2024 are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2025</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,657</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2026</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">643,157</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2027</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2028</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">580,091</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2029</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">360</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt and mortgage maturities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,253,062</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion included in other current liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(165</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Fixed and determinable interest</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(36,511</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(13,981</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,202,405</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseInformationTableTextBlock', window );">Amounts Related to Operating Leases</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At December 31, 2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use operating lease assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">161.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">170.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average remaining lease term</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.1 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average discount rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock', window );">Future Payments for Operating Lease Liabilities</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2024,
    the future payments for our operating lease liabilities are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</span> <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</span></div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Year ending December 31,</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,870</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2026</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,032</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2027</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,054</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2028</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,973</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2029</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,687</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">157,622</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total minimum lease payments</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">260,238</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: left; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Imputed interest</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(89,369</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion (included in <span style="-sec-ix-hidden:Fact_9874929ec96442469df0f0fc39baed32">other current liabilities</span>)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,064</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">161,805</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherNoncurrentLiabilitiesTableTextBlock', window );">Liability Related to Sale of Future Royalties</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our liability related to
      sale of future royalties for the year ended </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands):</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of future royalties in January 2023</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">500,000</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance costs related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,434</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty payments to Royalty Pharma</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(44,628</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68,238</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">560</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of December 31, 2023</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">513,736</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty payments to Royalty Pharma</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(44,981</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,846</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">611</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of December 31, 2024</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">542,212</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ConvertibleNotesDisclosureLineItems', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtTableTextBlock', window );">Convertible Senior Notes</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2024, we had the
    following 1.75% Notes outstanding (in millions, except interest rate and price per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.75% Notes</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">575.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_6bfb094eab7041389566a848570cbbe5">June 2028</span></div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.75</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.73</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ConvertibleNotesDisclosureLineItems', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtTableTextBlock', window );">Convertible Senior Notes</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2024, we had the
    following 0% Notes outstanding (in millions, except interest rate and price per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">0% Notes</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_77100aa329424b42b6f03dc4fa1e2472">April 2026</span></div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.84</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.39</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of information on lessee's operating leases, including carrying value of right-of-use assets and lease liabilities, weighted-average remaining term and weighted-average discount rate.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of contractual obligation by timing of payment due. Includes, but is not limited to, long-term debt obligation, lease obligation, and purchase obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Name Regulation S-X (SX)<br> -Number 210<br> -Section 12<br> -Subsection 04<br> -Subparagraph (a)<br> -Publisher SEC<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of convertible debt instrument. Includes, but is not limited to, principal amount and amortized premium or discount.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of undiscounted cash flows of lessee's operating lease liability. Includes, but is not limited to, reconciliation of undiscounted cash flows to operating lease liability recognized in statement of financial position.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-6<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of other noncurrent liabilities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of long-debt instruments or arrangements, including identification, terms, features, collateral requirements and other information necessary to a fair presentation. These are debt arrangements that originally required repayment more than twelve months after issuance or greater than the normal operating cycle of the entity, if longer.</p></div>
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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,692</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Exercisable at December 31, 2024</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,089</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49.85</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.66</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,460</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfSharebasedCompensationRestrictedStockAndRestrictedStockUnitsActivityTableTextBlock', window );">Restricted Stock Unit Activity</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the RSU activity for the year ended December 31, 2024 (in thousands, except per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Grant Date Fair</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2023</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,239</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43.40</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,005</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.92</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,185</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.88</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(228</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.83</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2024</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,831</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.06</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationPerformanceSharesAwardUnvestedActivityTableTextBlock', window );">Performance Restricted Stock Unit Activity</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the PRSU activity for the year ended December 31, 2024 (in thousands, except per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Grant Date Fair</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2023</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">226</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.04</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">179</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">78.41</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(73</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.35</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(25</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68.21</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2024</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">307</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66.72</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock', window );">Stock-Based Compensation Expense</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the years ended December 31, 2024, 2023 and 2022 (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">767</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">499</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">533</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">92,403</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,826</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">73,704</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37,030</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,484</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,027</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense, net of amounts capitalized</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130,200</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105,809</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100,264</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Capitalized stock-based compensation expense</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">799</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stock-based compensation expense</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130,999</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105,809</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100,264</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for Stock Options</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Options:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.3 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.3 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.3 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Board of Director Stock Options:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.5 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.7 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.4 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for ESPP</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">ESPP:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(334,707</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(258,493</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">644</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">742</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">508</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss before income taxes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(460,068</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(333,965</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(257,985</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock', window );">Income Tax Expense (Benefit)</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our income tax expense (benefit) was as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Federal</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,492</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35,861</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,522</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(848</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,687</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,129</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">169</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">147</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current income tax expense (benefit)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,171</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,321</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Federal</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total income tax expense (benefit)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,171</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,321</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfEffectiveIncomeTaxRateReconciliationTableTextBlock', window );">Reconciliation of Statutory to Effective Tax Rate</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to loss before income taxes. The sources
    and tax effects of the differences are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="22" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pre-tax loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(460,068</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(333,965</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(257,985</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Statutory rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(96,614</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(70,133</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(54,177</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State income tax net of federal benefit</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(11,889</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net change in valuation allowance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">152,590</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(33.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">175,388</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(52.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,951</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax credits</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(53,497</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(67,131</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(39,729</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax rate change</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,815</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2.4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,091</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-deductible compensation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,895</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,814</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.2</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">327</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.1</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,493</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.2</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,732</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19,546</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,030</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5.4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">665</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(401</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">344</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,171</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,321</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfDeferredTaxAssetsAndLiabilitiesTableTextBlock', window );">Deferred Tax Assets and Liabilities</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Significant components of our deferred tax assets and liabilities as of December 31, 2024 and 2023 are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95,851</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,063</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,683</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82,660</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,468</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intangible and capital assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">93,541</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,380</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,310</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,849</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Capitalized research and development expenses</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">323,560</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">238,738</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,481</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43,718</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sale of future royalties</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">148,918</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">144,608</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,343</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total deferred tax assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,174,111</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,025,713</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred Tax Liabilities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Fixed assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,719</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,166</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(36,788</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(42,007</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,896</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,910</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net deferred tax asset</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,129,708</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">977,630</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Valuation allowance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,129,708</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(977,630</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total net deferred tax assets and liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock', window );">Gross Unrecognized Tax Benefits</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our gross unrecognized tax benefits <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(in thousands):</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance of unrecognized tax benefits</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43,298</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56,567</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55,085</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Decrease for lapse of statute of limitations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,579</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14,993</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Decrease for prior period tax positions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(110</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(267</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for prior period tax positions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,902</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">429</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">259</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for current period tax positions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,650</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,032</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,490</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance of unrecognized tax benefits</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,161</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43,298</div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br></p></div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">527,259</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,229</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19,454</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,948</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57,729</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,293</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76,162</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D support</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82,559</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81,019</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59,840</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">230,478</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">205,135</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">124,370</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other segment items (1)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">109,016</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">118,365</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(40,205</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consolidated net loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(453,897</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(366,286</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(269,722</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other segment items include stock-based compensation expense, investment income, interest expense, gain or loss on investments, other income or expense and income tax expense or benefit.&#160;</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the profit or loss and total assets for each reportable segment. An entity discloses certain information on each reportable segment if the amounts (a) are included in the measure of segment profit or loss reviewed by the chief operating decision maker or (b) are otherwise regularly provided to the chief operating decision maker, even if not included in that measure of segment profit or loss.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 25<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-25<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fourth Quarter Financial Data (Unaudited) (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following financial information reflects all normal recurring adjustments, which are, in the opinion of management, necessary for a
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31,</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">226,577</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">324,505</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

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    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">337,398</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">330,627</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

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    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss from operations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(110,821</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,122</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(104,349</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share (3) (4)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.66</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.06</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

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    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Diluted net loss per share (3) (5)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.66</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.06</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue was lower in the three months ended December 31, 2024 compared to the same period in 2023 primarily due to significant partner payments earned in the fourth quarter of 2023, including the $</span>50<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment we earned from AstraZeneca when the FDA
              approved WAINUA for ATTRv-PN in the U.S., $</span>36<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
              million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis. </span>In addition, WAINUA
            joint development revenue decreased in the three months ended December 31, 2024 compared to the same period in 2023 as development activities relating to ATTRv-PN wound down with the launch of WAINUA.</div>
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<div><br/>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses were relatively consistent in the three months
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        </td>

  </tr>


</table>

<div><br/>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </span>compute net loss per share independently for each quarter during <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</span></div>
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<div><br/>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies, </span>we compute basic net loss per share by dividing the total net loss by our weighted-average number of common shares outstanding
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<div><br/>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incurred a net loss for the fourth quarter of 2024 and 2023. As a
            result, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive.</div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of quarterly financial data. Includes, but is not limited to, financial information for fiscal quarters, cumulative effect of a change in accounting principle and earnings per share data.</p></div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45368027043744">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Organization and Business Activity (Details)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th">
<div>Dec. 31, 2024 </div>
<div>Segment</div>
</th></tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Organization and Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NumberOfOperatingSegments', window );">Number of operating segments</a></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of operating segments. An operating segment is a component of an enterprise: (a) that engages in business activities from which it may earn revenues and incur expenses (including revenues and expenses relating to transactions with other components of the same enterprise), (b) whose operating results are regularly reviewed by the enterprise's chief operating decision maker to make decisions about resources to be allocated to the segment and assess its performance, and (c) for which discrete financial information is available. An operating segment may engage in business activities for which it has yet to earn revenues, for example, start-up operations may be operating segments before earning revenues.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 49<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-49<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-18<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NumberOfOperatingSegments</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367926155088">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Contracts Receivable (Details)<br></strong></div></th>
<th class="th" colspan="2">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>qtr </div>
<div>Partner</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>Partner</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractReceivablesAbstract', window );"><strong>Contracts Receivable [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfQuartersAfterBillingWhenPaymentIsReceived', window );">Number of quarters after billing when payment is received | qtr</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrentAbstract', window );"><strong>Contracts Receivable [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfSignificantCustomers', window );">Number of significant customers | Partner</a></td>
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<td class="nump">1<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember', window );">Contracts Receivables [Member] | Credit Concentration [Member] | Three Significant Customers [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrentAbstract', window );"><strong>Contracts Receivable [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember', window );">Contracts Receivables [Member] | Credit Concentration [Member] | One Significant Customer [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrentAbstract', window );"><strong>Contracts Receivable [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of quarters after billing when payment is received from the Company's partner or customer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of significant customers with which the Company does business.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<body>
<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367927055664">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Deferred Revenue (Details) - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="2">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
</tr>
<tr class="re">
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityRevenueRecognized', window );">Revenue recognized from amounts in beginning deferred revenue balance</a></td>
<td class="nump">$ 166.1<span></span>
</td>
<td class="nump">$ 78.2<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityRevenueRecognized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of revenue recognized that was previously included in balance of obligation to transfer good or service to customer for which consideration from customer has been received or is due.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityRevenueRecognized</td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
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<head>
<title></title>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929341856">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Research, Development and Patent Expenses (Details) - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpenseAbstract', window );"><strong>Research, Development and Patent Expenses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PatentExpenses', window );">Patent expenses</a></td>
<td class="nump">$ 5.3<span></span>
</td>
<td class="nump">$ 4.3<span></span>
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<td class="nump">$ 4.7<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Includes charges for amortization and write-downs of capitalized patent costs as well as legal fees for patent litigation and patent defense.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PatentExpenses</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchAndDevelopmentExpenseAbstract</td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367928978048">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details)<br></strong></div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic and Diluted Net Loss Per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic and Diluted Net Loss Per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
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<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic and Diluted Net Loss Per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<link rel="stylesheet" type="text/css" href="include/report.css">
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<body>
<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929208240">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Stock-Based Compensation Expense (Details)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th">
<div>Dec. 31, 2024 </div>
<div>Period </div>
<div>shares</div>
</th></tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member', window );">Stock Options Granted Prior to January 1, 2022 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">7 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember', window );">Stock Options Granted on January 1, 2022 and Thereafter [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">10 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Employees [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [Member] | Granted Prior to June 2020 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [Member] | Granted After June 2020 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">1 year<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [Member] | Granted at Initial Appointment [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">3 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_TermOfAlternativePayoutMechanism', window );">Term of Alternative Calculation</a></td>
<td class="text">3 years<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MeasurementPeriodForAlternativePayoutMechanism', window );">Measurement period for Alternative Calculation</a></td>
<td class="text">3 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods', window );">Number of performance periods | Period</a></td>
<td class="nump">3<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">3 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | One-Year Period [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">1 year<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Two-Year Period [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">2 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Three-Year Period [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">3 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Granted 2020 through 2022 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest', window );">Number of units guaranteed to vest (in shares)</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Granted 2020 through 2022 [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Granted 2020 through 2022 [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="nump">150.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Granted 2020 through 2022 [Member] | One-Year Period [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">33.30%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Granted 2020 through 2022 [Member] | Two-Year Period [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">33.30%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Granted 2020 through 2022 [Member] | Three-Year Period [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">33.30%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Granted in 2024 and 2023 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">100.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest', window );">Number of units guaranteed to vest (in shares)</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Granted in 2024 and 2023 [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Granted in 2024 and 2023 [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="nump">200.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MeasurementPeriodForAlternativePayoutMechanism">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Measurement period for alternative payout mechanism, or the Alternative Calculation, included in equity-based award, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MeasurementPeriodForAlternativePayoutMechanism</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of separate performance periods under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of units guaranteed to vest under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of units guaranteed to vest under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_TermOfAlternativePayoutMechanism">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of an alternative three-year payout mechanism, or the Alternative Calculation, included in equity-based award, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_TermOfAlternativePayoutMechanism</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period over which grantee's right to exercise award under share-based payment arrangement is no longer contingent on satisfaction of service or performance condition, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days. Includes, but is not limited to, combination of market, performance or service condition.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of vesting of award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period from grant date that an equity-based award expires, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GranteeStatusAxis=us-gaap_ShareBasedPaymentArrangementEmployeeMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GranteeStatusAxis=us-gaap_ShareBasedPaymentArrangementEmployeeMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GranteeStatusAxis=ions_ShareBasedPaymentArrangementBoardOfDirectorsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GranteeStatusAxis=ions_ShareBasedPaymentArrangementBoardOfDirectorsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardDateAxis=ions_GrantedPriorToJune2020Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_GrantedPriorToJune2020Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardDateAxis=ions_GrantedAfterJune2020Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_GrantedAfterJune2020Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardDateAxis=ions_GrantedAtInitialAppointmentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_GrantedAtInitialAppointmentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GranteeStatusAxis=srt_ExecutiveOfficerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GranteeStatusAxis=srt_ExecutiveOfficerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheOneMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheOneMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheTwoMember">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheTwoMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheThreeMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheThreeMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardDateAxis=ions_Granted2020Through2022Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_Granted2020Through2022Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardDateAxis=ions_GrantedIn2024And2023Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_GrantedIn2024And2023Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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</table></div>
</div></td></tr>
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</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>59
<FILENAME>R42.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929573536">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)<br></strong></div></th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>Company</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract', window );"><strong>Cash, Cash Equivalents and Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of publicly held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">3<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of privately held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">7<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of privately-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for under the cost method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of publicly-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for at fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>60
<FILENAME>R43.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
							function toggleNextSibling (e) {
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<body>
<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367926864976">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Property, Plant and Equipment (Details)<br></strong></div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember', window );">Computer Software, Laboratory, Manufacturing and Other Equipment [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">3 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember', window );">Computer Software, Laboratory, Manufacturing and Other Equipment [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">10 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember', window );">Building, Building Improvements and Building Systems [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">15 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember', window );">Building, Building Improvements and Building Systems [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">40 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandImprovementsMember', window );">Land Improvements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">20 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember', window );">Leasehold Improvements [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">5 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember', window );">Leasehold Improvements [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">15 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember', window );">Furniture and Fixtures [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">5 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember', window );">Furniture and Fixtures [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">10 years<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentUsefulLife">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Useful life of long lived, physical assets used in the normal conduct of business and not intended for resale, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days. Examples include, but not limited to, land, buildings, machinery and equipment, office equipment, furniture and fixtures, and computer equipment.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentUsefulLife</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandImprovementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929214896">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Convertible Debt (Details) - Note<br></strong></div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentNumberOfConvertibleNotes', window );">Number of outstanding convertible notes</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentNumberOfConvertibleNotes">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of outstanding convertible notes.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentNumberOfConvertibleNotes</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367932729008">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Call Spread (Details)<br></strong></div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">0.00%<span></span>
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<td class="nump">0.00%<span></span>
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<td class="nump">0.00%<span></span>
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<td class="nump">0.00%<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GeneralDiscussionOfDerivativeInstrumentsAndHedgingActivitiesAbstract', window );"><strong>Call Spread [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
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<td class="nump">0.125%<span></span>
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<td class="nump">0.125%<span></span>
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<td class="text">&#160;<span></span>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367930788320">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Supplemental Financial Data, Inventories (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
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<tr class="re">
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryRawMaterials', window );">Raw materials</a></td>
<td class="nump">$ 5,557<span></span>
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<td class="nump">$ 1,810<span></span>
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<td class="nump">6,679<span></span>
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<td class="nump">5,477<span></span>
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<td class="nump">276<span></span>
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<td class="nump">154<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryNet', window );">Total inventories</a></td>
<td class="nump">$ 12,512<span></span>
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<td class="nump">$ 7,441<span></span>
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<div style="display: none;">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before valuation and LIFO reserves of completed merchandise or goods expected to be sold within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after valuation and LIFO reserves of inventory expected to be sold, or consumed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483467/210-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before valuation and LIFO reserves of raw materials expected to be sold, or consumed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryRawMaterials</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before valuation and LIFO reserves of merchandise or goods in the production process expected to be completed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryWorkInProcess</td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367928081312">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Supplemental Financial Data, Property, Plant and Equipment (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment', window );">Less accumulated depreciation</a></td>
<td class="num">$ (106,316)<span></span>
</td>
<td class="num">$ (96,759)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="nump">94,251<span></span>
</td>
<td class="nump">71,043<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PropertyPlantAndEquipmentExcludingLandMember', window );">Property, Plant and Equipment, Excluding Land [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">191,998<span></span>
</td>
<td class="nump">159,233<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="nump">85,682<span></span>
</td>
<td class="nump">62,474<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember', window );">Computer Software, Laboratory, Manufacturing and Other Equipment [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">86,540<span></span>
</td>
<td class="nump">79,885<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember', window );">Building, Building Improvements and Building Systems [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">41,228<span></span>
</td>
<td class="nump">41,228<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember', window );">Leasehold Improvements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">54,375<span></span>
</td>
<td class="nump">28,276<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember', window );">Furniture and Fixtures [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">9,855<span></span>
</td>
<td class="nump">9,844<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember', window );">Land [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">$ 8,569<span></span>
</td>
<td class="nump">$ 8,569<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated depreciation, depletion and amortization for physical assets used in the normal conduct of business to produce goods and services.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(14))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482099/360-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentAbstract</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before accumulated depreciation, depletion and amortization of physical assets used in the normal conduct of business and not intended for resale. Examples include, but are not limited to, land, buildings, machinery and equipment, office equipment, and furniture and fixtures.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(13))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 360<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482099/360-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentGross</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after accumulated depreciation, depletion and amortization of physical assets used in the normal conduct of business to produce goods and services and not intended for resale. Examples include, but are not limited to, land, buildings, machinery and equipment, office equipment, and furniture and fixtures.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 360<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482099/360-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7A<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-7A<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 360<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478451/942-360-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentNet</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PropertyPlantAndEquipmentExcludingLandMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>65
<FILENAME>R48.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
							function toggleNextSibling (e) {
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</head>
<body>
<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931364288">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Supplemental Financial Data, Accrued Liabilities (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrentAbstract', window );"><strong>Accrued Liabilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AccruedClinicalDevelopmentExpenses', window );">Clinical expenses</a></td>
<td class="nump">$ 77,436<span></span>
</td>
<td class="nump">$ 105,967<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AccruedInLicensingFeesCurrent', window );">In-licensing expenses</a></td>
<td class="nump">7,951<span></span>
</td>
<td class="nump">7,454<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AccruedCommercialExpensesCurrent', window );">Commercial expenses</a></td>
<td class="nump">3,589<span></span>
</td>
<td class="nump">4,875<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherAccruedLiabilitiesCurrent', window );">Other miscellaneous expenses</a></td>
<td class="nump">19,462<span></span>
</td>
<td class="nump">29,598<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrent', window );">Total accrued liabilities</a></td>
<td class="nump">$ 108,438<span></span>
</td>
<td class="nump">$ 147,894<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedClinicalDevelopmentExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred through that date and payable for clinical development expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AccruedClinicalDevelopmentExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedCommercialExpensesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred through that date and payable for commercial expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AccruedCommercialExpensesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedInLicensingFeesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred through that date and payable for in-licensing fees under collaboration agreements. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AccruedInLicensingFeesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred and payable, pertaining to costs that are statutory in nature, are incurred on contractual obligations, or accumulate over time and for which invoices have not yet been received or will not be rendered. Examples include taxes, interest, rent and utilities. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedLiabilitiesCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedLiabilitiesCurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAccruedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of expenses incurred but not yet paid classified as other, due within one year or the normal operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherAccruedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>66
<FILENAME>R49.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
							function toggleNextSibling (e) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
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</head>
<body>
<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929580864">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Revenues (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="4">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Component</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 705,138<span></span>
</td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_CommercialMember', window );">Commercial Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">293,076<span></span>
</td>
<td class="nump">308,591<span></span>
</td>
<td class="nump">303,358<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember', window );">SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">216,090<span></span>
</td>
<td class="nump">240,379<span></span>
</td>
<td class="nump">242,314<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_WainusRoyaltiesMember', window );">WAINUA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">20,207<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_OtherCommercialMember', window );">Other Commercial Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">56,779<span></span>
</td>
<td class="nump">68,212<span></span>
</td>
<td class="nump">61,044<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=us-gaap_ProductMember', window );">TEGSEDI and WAYLIVRA Revenue, Net [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">34,189<span></span>
</td>
<td class="nump">34,913<span></span>
</td>
<td class="nump">30,051<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_OtherMember', window );">Other Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">22,590<span></span>
</td>
<td class="nump">33,299<span></span>
</td>
<td class="nump">30,993<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember', window );">Research and Development Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">412,062<span></span>
</td>
<td class="nump">479,056<span></span>
</td>
<td class="nump">284,009<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_CollaborativeAgreementRevenueMember', window );">Collaborative Agreement Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">332,647<span></span>
</td>
<td class="nump">352,657<span></span>
</td>
<td class="nump">207,222<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_WainuaJointDevelopmentRevenueMember', window );">WAINUA Joint Development Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">79,415<span></span>
</td>
<td class="nump">126,399<span></span>
</td>
<td class="nump">$ 76,787<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology Collaboration with Biogen [Member] | QALSODY [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember', window );">WAINUA (Eplontersen) Collaboration with AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 20,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfMaterialComponents', window );">Number of material components | Component</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner', window );">Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca</a></td>
<td class="nump">55.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfMaterialComponents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of material components identified in the collaboration agreement under Accounting Standards Codification (ASC) 808, Collaborative Arrangements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfMaterialComponents</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of costs associated with the ongoing global Phase 3 development program paid by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_WainusRoyaltiesMember</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember</td>
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<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="5">12 Months Ended</th>
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<div>Dec. 31, 2024 </div>
<div>USD ($)</div>
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<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($)</div>
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<th class="th">
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<div>USD ($)</div>
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<div>USD ($)</div>
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<div>USD ($) </div>
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<div>Dec. 31, 2015 </div>
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</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 705,138<span></span>
</td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember', window );">AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">129,759<span></span>
</td>
<td class="nump">202,236<span></span>
</td>
<td class="nump">$ 79,160<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember', window );">AstraZeneca [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">18.00%<span></span>
</td>
<td class="nump">26.00%<span></span>
</td>
<td class="nump">13.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember', window );">WAINUA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="nump">3,600,000<span></span>
</td>
<td class="nump">$ 3,600,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="nump">485,000<span></span>
</td>
<td class="nump">485,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="nump">2,900,000<span></span>
</td>
<td class="nump">$ 2,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates', window );">Royalty percentage received on sales of medicine in U.S.</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfMaterialComponents', window );">Number of material components | Component</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner', window );">Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">55.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 20,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember', window );">WAINUA [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="nump">200,000<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember', window );">WAINUA [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">465,000<span></span>
</td>
<td class="nump">465,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="nump">115,000<span></span>
</td>
<td class="nump">115,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember', window );">WAINUA [Member] | ATTRv-PN [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember', window );">Cardiovascular, Renal and Metabolic Diseases [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="nump">4,300,000<span></span>
</td>
<td class="nump">4,300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="nump">175,000<span></span>
</td>
<td class="nump">175,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="nump">514,000<span></span>
</td>
<td class="nump">514,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="nump">863,000<span></span>
</td>
<td class="nump">863,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="nump">2,800,000<span></span>
</td>
<td class="nump">2,800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="nump">30,000<span></span>
</td>
<td class="nump">30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 65,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="nump">90,000<span></span>
</td>
<td class="nump">$ 90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember', window );">Cardiovascular, Renal and Metabolic Diseases [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember', window );">Cardiovascular, Renal and Metabolic Diseases [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 340,000<span></span>
</td>
<td class="nump">$ 340,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of sales milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPaymentToBeAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfMaterialComponents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of material components identified in the collaboration agreement under Accounting Standards Codification (ASC) 808, Collaborative Arrangements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfMaterialComponents</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of costs associated with the ongoing global Phase 3 development program paid by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a medicine by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on sales of a medicine in the United States by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
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<td><strong> Balance Type:</strong></td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367932293088">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Biogen (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="5">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jan. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Apr. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2012 </div>
<div>PerformanceObligation</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 705,138<span></span>
</td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaMember', window );">SPINRAZA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid', window );">Maximum amount of annual sales on which royalty payments are paid</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaMember', window );">SPINRAZA [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid to Royalty Pharma on annual sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 475,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 475,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaMember', window );">SPINRAZA [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid to Royalty Pharma on annual sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 550,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 550,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember', window );">SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">216,090<span></span>
</td>
<td class="nump">240,379<span></span>
</td>
<td class="nump">242,314<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">368,058<span></span>
</td>
<td class="nump">350,146<span></span>
</td>
<td class="nump">$ 366,696<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 211,000<span></span>
</td>
<td class="nump">$ 307,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">52.00%<span></span>
</td>
<td class="nump">44.00%<span></span>
</td>
<td class="nump">62.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationSpinrazaMember', window );">SPINRAZA [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationSpinrazaMember', window );">SPINRAZA [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationSpinrazaMember', window );">SPINRAZA [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationSpinrazaMember', window );">SPINRAZA [Member] | SPINRAZA R&amp;D Revenue [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">425,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013NeurologyMember', window );">2013 Neurology [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 110,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013NeurologyMember', window );">2013 Neurology [Member] | QALSODY [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013NeurologyMember', window );">2013 Neurology [Member] | QALSODY [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013NeurologyMember', window );">2013 Neurology [Member] | QALSODY Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 3,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013NeurologyMember', window );">2013 Neurology [Member] | QALSODY R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">108,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember', window );">New Antisense Medicines for the Treatment of SMA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 85,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember', window );">New Antisense Medicines for the Treatment of SMA [Member] | ION306 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">555,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">110,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">400,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2018NeurologyMember', window );">2018 Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 375,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 552,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PremiumPaidOnSharesPurchased', window );">Premium paid on shares purchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 177,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">623,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration', window );">Maximum amount of payments receivable per medicine over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">270,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration', window );">Maximum amount of license fees per medicine over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration', window );">Maximum amount of development milestone payments per medicine over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">105,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments per medicine over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2012NeurologyMember', window );">2012 Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">185,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 30<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2012NeurologyMember', window );">2012 Neurology [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">230,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2012NeurologyMember', window );">2012 Neurology [Member] | IONIS-MAPT [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">57,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2012NeurologyMember', window );">2012 Neurology [Member] | ION582 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 68,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of annual sales on which royalty payments are paid under the royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received for each medicine that achieves marketing approval over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received for each medicine that achieves marketing approval over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive for each medicine that achieves marketing approval over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received for each medicine that achieves marketing approval over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of sales milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Maximum royalty payments under the royalty purchase agreement made before royalty interest reverts back to the Company.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPaymentToBeAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of royalty payments paid on annual sales of medicine.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PremiumPaidOnSharesPurchased">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash premium paid on the purchase of the Company's common stock under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PremiumPaidOnSharesPurchased</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a medicine by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_SpinrazaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_SpinrazaMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationSpinrazaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationSpinrazaMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_SpinrazaResearchAndDevelopmentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_SpinrazaResearchAndDevelopmentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013NeurologyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013NeurologyMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_QalsodyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_QalsodyMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_QalsodyResearchAndDevelopmentMember</td>
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<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember</td>
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<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_Ion306Member</td>
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<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2018NeurologyMember</td>
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<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2012NeurologyMember</td>
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<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_IonisMaptMember</td>
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<head>
<title></title>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929583904">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, GSK (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="4">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2010</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 705,138<span></span>
</td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember', window );">GSK [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 35,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="nump">260,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="nump">42,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="nump">120,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="nump">15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">15,000<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember', window );">GSK [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">2.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember', window );">GSK [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 105,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of sales milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPaymentToBeAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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</div>
</body>
</html>
</TEXT>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>70
<FILENAME>R53.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<html>
<head>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367921246048">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Novartis (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="4">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Aug. 31, 2023 </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Mar. 31, 2017 </div>
<div>PerformanceObligation</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 705,138<span></span>
</td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_PelacarsenActivePharmaceuticalIngredientMember', window );">Pelacarsen API [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid to Royalty Pharma on annual sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationsMember', window );">Novartis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 37,762<span></span>
</td>
<td class="nump">30,194<span></span>
</td>
<td class="nump">$ 237<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="nump">$ 4,200<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationsMember', window );">Novartis [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5.00%<span></span>
</td>
<td class="nump">4.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationsMember', window );">Novartis [Member] | Maximum [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationPelacarsenMember', window );">Pelacarsen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">290,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">360,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">275,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">50,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">108,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PremiumReceivedOnSharesIssued', window );">Premium received on shares issued</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">28,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture', window );">Potential premium received if common stock was purchased in the future</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 5,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 104,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationPelacarsenMember', window );">Pelacarsen [Member] | Pelacarsen API [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember', window );">Lp(a)-Driven Cardiovascular Disease [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 730,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">155,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">105,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">410,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember', window );">Lp(a)-Driven Cardiovascular Disease [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember', window );">Lp(a)-Driven Cardiovascular Disease [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of sales milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPaymentToBeAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of royalty payments paid on annual sales of medicine.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The potential premium received if common stock was purchased in the future under a Stock Purchase Agreement (SPA) in conjunction with the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PremiumReceivedOnSharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The total amount of the premium received over the trading price of common stock at the time of purchase.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PremiumReceivedOnSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a medicine by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_PelacarsenActivePharmaceuticalIngredientMember</td>
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<tr><td><div class="body" style="padding: 2px;">
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<td><strong> Period Type:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<tr>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367925698560">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Roche (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($) </div>
<div>Program</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Oct. 31, 2018 </div>
<div>PerformanceObligation</div>
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<th class="th">
<div>Dec. 31, 2013 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
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<td class="nump">$ 705,138<span></span>
</td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">39,871<span></span>
</td>
<td class="nump">48,838<span></span>
</td>
<td class="nump">$ 67,202<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="nump">$ 36,700<span></span>
</td>
<td class="nump">$ 7,700<span></span>
</td>
<td class="nump">$ 36,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6.00%<span></span>
</td>
<td class="nump">6.00%<span></span>
</td>
<td class="nump">11.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember', window );">Sefaxersen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 430,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 280,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 140,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">23,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">97,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationHuntingtonsDiseaseMember', window );">HD [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">395,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration', window );">Maximum amount of upfront payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">170,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">80,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration', window );">Maximum amount of milestone payments for each additional medicine successfully developed over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">136,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 17,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationRNATargetedProgramsForADAndHDMember', window );">RNA-targeted Programs for AD and HD [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfEarlyStagePrograms', window );">Number of early-stage programs | Program</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 625,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">167,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">398,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationRNATargetedProgramsForADAndHDMember', window );">RNA-targeted Programs for AD and HD [Member] | R&amp;D Services for Investigational Medicine for AD [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationRNATargetedProgramsForADAndHDMember', window );">RNA-targeted Programs for AD and HD [Member] | R&amp;D Services for Investigational Medicine for HD [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of milestone payments to be received for each medicine that is successfully developed over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of sales milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of upfront payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPaymentToBeAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfEarlyStagePrograms">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of early-stage programs to be developed for RNA-targeting investigational medicines for the treatment of Alzheimer's disease (AD) and Huntington's disease (HD).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfEarlyStagePrograms</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a medicine by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationHuntingtonsDiseaseMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationHuntingtonsDiseaseMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationRNATargetedProgramsForADAndHDMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationRNATargetedProgramsForADAndHDMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Otsuka (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
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<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($)</div>
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<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($)</div>
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<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
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<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 705,138<span></span>
</td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_OtsukaCollaborationsMember', window );">Otsuka [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">46,856<span></span>
</td>
<td class="nump">56,480<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="nump">$ 6,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 6,700<span></span>
</td>
<td class="nump">$ 8,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_OtsukaCollaborationsMember', window );">Otsuka [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">7.00%<span></span>
</td>
<td class="nump">7.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_OtsukaCollaborationDonidalorsenMember', window );">Donidalorsen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 20,000<span></span>
</td>
<td class="nump">$ 20,000<span></span>
</td>
<td class="nump">$ 65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="nump">290,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">290,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration', window );">Maximum amount of upfront payments over term of collaboration</a></td>
<td class="nump">85,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">85,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="nump">65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="nump">140,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">140,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="nump">15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 85,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">95,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 95,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_OtsukaCollaborationDonidalorsenMember', window );">Donidalorsen [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">30.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_OtsukaCollaborationDonidalorsenMember', window );">Donidalorsen [Member] | License of Donidalorsen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">73,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_OtsukaCollaborationDonidalorsenMember', window );">Donidalorsen [Member] | R&amp;D Services for Donidalorsen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 11,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of sales milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of upfront payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPaymentToBeAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a medicine by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_OtsukaCollaborationsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_OtsukaCollaborationsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_OtsukaCollaborationDonidalorsenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_OtsukaCollaborationDonidalorsenMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
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<td><strong> Name:</strong></td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367926216912">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, PTC Therapeutics (Details)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of each medicine from the collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45368017010048">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Bicycle Therapeutics (Details) - Bicycle License Agreement [Member] - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="2">12 Months Ended</th>
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<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 42.0<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 34.8<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Acquisition of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period after completion of initial public offering by an equity investee and restriction to sell equity holding in the investee, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Represents the cash outflow for payments made under the collaboration agreement for the reimbursement of support received in connection with the Company's Huntington's disease program.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of expense for research and development. Includes, but is not limited to, cost for computer software product to be sold, leased, or otherwise marketed and writeoff of research and development assets acquired in transaction other than business combination or joint venture formation or both. Excludes write-down of intangible asset acquired in business combination or from joint venture formation or both, used in research and development activity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 48<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-48<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 985<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481283/985-20-50-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 730<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482916/730-10-50-1<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 912<br> -SubTopic 730<br> -Name Accounting Standards Codification<br> -Section 25<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479532/912-730-25-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929281520">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Metagenomi (Details) - Metagenomi [Member]<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </div>
<div>Target</div>
</th></tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized', window );">Number of targets to be researched, developed and commercialized | Target</a></td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized', window );">Number of additional targets to be researched, developed and commercialized | Target</a></td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PaymentToLicenseTechnology', window );">Payment to license technology | $</a></td>
<td class="nump">$ 80<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost', window );">Research and development expense | $</a></td>
<td class="nump">$ 80<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of additional targets to be researched, developed and commercialized under the collaboration agreement upon achievement of certain development milestones.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of targets to be researched, developed and commercialized under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PaymentToLicenseTechnology">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to license technology under a collaboration and license agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PaymentToLicenseTechnology</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of expense for research and development. Excludes cost for computer software product to be sold, leased, or otherwise marketed, writeoff of research and development assets acquired in transaction other than business combination or joint venture formation or both, and write-down of intangible asset acquired in business combination or from joint venture formation or both, used in research and development activity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 730<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482916/730-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost</td>
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<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_MetagenomiLicenseAgreementMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_MetagenomiLicenseAgreementMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931365168">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Alnylam Pharmaceuticals, Inc. (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="4">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2015 </div>
<div>Target </div>
<div>Program</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue | $</a></td>
<td class="nump">$ 705,138<span></span>
</td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember', window );">Alnylam [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfTherapeuticPrograms', window );">Number of therapeutic programs | Program</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement', window );">Number of therapeutic targets granted to Ionis | Target</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement', window );">Number of unnamed therapeutic targets granted to Ionis | Target</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement', window );">Number of therapeutic targets granted by Ionis | Target</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue | $</a></td>
<td class="nump">8,110<span></span>
</td>
<td class="nump">28,426<span></span>
</td>
<td class="nump">$ 21,389<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred contract revenue | $</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember', window );">Alnylam [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">4.00%<span></span>
</td>
<td class="nump">4.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfTherapeuticPrograms">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of therapeutic programs with exclusive license rights under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTherapeuticPrograms</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of therapeutic targets granted by the partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of therapeutic targets granted to the partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of unnamed therapeutic targets granted by the partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367928083568">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments, Contract Maturity of Available-for-Sale Securities (Details)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2024</div></th></tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract', window );"><strong>Contract Maturity of Available-for-Sale Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage', window );">One year or less</a></td>
<td class="nump">69.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage', window );">After one year but within two years</a></td>
<td class="nump">24.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage', window );">After two years but within three and a half years</a></td>
<td class="nump">7.00%<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage', window );">Total</a></td>
<td class="nump">100.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage', window );">Percentage of available-for-sale securities with a maturity of less than two years</a></td>
<td class="nump">93.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange1', window );">Maximum contract maturity period, range 1</a></td>
<td class="text">1 year<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange2', window );">Maximum contract maturity period, range 2</a></td>
<td class="text">2 years<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange3', window );">Maximum contract maturity period, range 3</a></td>
<td class="text">3 years 6 months<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature beyond one year but within two years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature beyond two years but within three and one-half years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate percentage of all available-for-sale debt securities, regardless of maturity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature within one year of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature within two years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the first range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange2">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the second range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange2</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange3">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the third range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange3</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367930161296">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Investments, Summary of Investments (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($) </div>
<div>Company</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsAllOtherInvestmentsAbstract', window );"><strong>Ownership Interests in Private and Public Companies [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of privately held companies in which there is an equity ownership interest of less than 20% | Company</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of publicly held companies in which there is an equity ownership interest of less than 20% | Company</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,402,258<span></span>
</td>
<td class="nump">$ 1,316,219<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,607<span></span>
</td>
<td class="nump">415<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(399)<span></span>
</td>
<td class="num">(5,238)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,403,466<span></span>
</td>
<td class="nump">1,311,396<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">654,600<span></span>
</td>
<td class="nump">651,628<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">984<span></span>
</td>
<td class="nump">3,063<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(3,042)<span></span>
</td>
<td class="num">(1,197)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">652,542<span></span>
</td>
<td class="nump">653,494<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Available-for-sale Debt Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,056,858<span></span>
</td>
<td class="nump">1,967,847<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,591<span></span>
</td>
<td class="nump">3,478<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(3,441)<span></span>
</td>
<td class="num">(6,435)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,056,008<span></span>
</td>
<td class="nump">1,964,890<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFVNIAbstract', window );"><strong>Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">35,012<span></span>
</td>
<td class="nump">35,012<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">25,027<span></span>
</td>
<td class="nump">25,237<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(13,753)<span></span>
</td>
<td class="num">(10,957)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">46,286<span></span>
</td>
<td class="nump">49,292<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract', window );"><strong>Available-for-sale Debt and Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,091,870<span></span>
</td>
<td class="nump">2,002,859<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">27,618<span></span>
</td>
<td class="nump">28,715<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(17,194)<span></span>
</td>
<td class="num">(17,392)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,102,294<span></span>
</td>
<td class="nump">2,014,182<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">593,810<span></span>
</td>
<td class="nump">559,967<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">487<span></span>
</td>
<td class="nump">157<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(240)<span></span>
</td>
<td class="num">(2,625)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">594,057<span></span>
</td>
<td class="nump">557,499<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">439,561<span></span>
</td>
<td class="nump">243,151<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">723<span></span>
</td>
<td class="nump">1,270<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(2,275)<span></span>
</td>
<td class="num">(692)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">438,009<span></span>
</td>
<td class="nump">243,729<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">143,647<span></span>
</td>
<td class="nump">224,711<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">287<span></span>
</td>
<td class="nump">64<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(39)<span></span>
</td>
<td class="num">(611)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">143,895<span></span>
</td>
<td class="nump">224,164<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">65,255<span></span>
</td>
<td class="nump">110,138<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">137<span></span>
</td>
<td class="nump">547<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(289)<span></span>
</td>
<td class="num">(21)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">65,103<span></span>
</td>
<td class="nump">110,664<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">657,285<span></span>
</td>
<td class="nump">513,784<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">825<span></span>
</td>
<td class="nump">152<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(120)<span></span>
</td>
<td class="num">(1,889)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">657,990<span></span>
</td>
<td class="nump">512,047<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">149,086<span></span>
</td>
<td class="nump">294,873<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">124<span></span>
</td>
<td class="nump">1,239<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(476)<span></span>
</td>
<td class="num">(480)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">148,734<span></span>
</td>
<td class="nump">295,632<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">7,516<span></span>
</td>
<td class="nump">17,757<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">8<span></span>
</td>
<td class="nump">42<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="num">(113)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">7,524<span></span>
</td>
<td class="nump">17,686<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,466<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">7<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(4)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,469<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember', window );">Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">698<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(2)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">696<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember', window );">Publicly Traded Equity Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFVNIAbstract', window );"><strong>Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">11,897<span></span>
</td>
<td class="nump">11,897<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">26<span></span>
</td>
<td class="nump">236<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(6,660)<span></span>
</td>
<td class="num">(5,832)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">5,263<span></span>
</td>
<td class="nump">6,301<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract', window );"><strong>Available-for-sale Debt and Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedLoss', window );">Unrealized loss on equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,000)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_EquitySecuritiesPrivateCompaniesMember', window );">Privately Held Equity Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFVNIAbstract', window );"><strong>Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">23,115<span></span>
</td>
<td class="nump">23,115<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">25,001<span></span>
</td>
<td class="nump">25,001<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(7,093)<span></span>
</td>
<td class="num">(5,125)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">41,023<span></span>
</td>
<td class="nump">$ 42,991<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract', window );"><strong>Available-for-sale Debt and Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedLoss', window );">Unrealized loss on equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">$ (2,000)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="3"></td></tr>
<tr><td colspan="3"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Includes investments classified as cash equivalents in our consolidated
            balance sheets.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Our publicly traded equity securities are included in other current
            assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2024, we recorded a $1.0 million net <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">unrealized loss in our consolidated statement of
              operations related to changes in the fair value of our investments in publicly traded companies.</span></td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at</span> cost minus impairments, plus or minus changes resulting from observable price changes in
            orderly transactions for the identical or similar investment of the same issuer, which are Level 3 inputs. In the year ended December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recorded a $</span>2.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million net unrealized loss in our consolidated statements of operations related to observable price changes of our investments in privately held companies.</span></td>
</tr>
</table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) cost of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Accumulated amount of unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Accumulated amount of unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of privately-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for under the cost method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of publicly-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for at fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 103<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482078/820-10-55-103<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 100<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482078/820-10-55-100<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-1<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(12))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483467/210-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482736/825-10-45-1A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNi</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cost of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI). Excludes equity method investment and investment in equity security without readily determinable fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 321<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479536/321-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNiUnrealizedLoss</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367926174864">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Investments, Investments Temporarily Impaired (Details)<br> $ in Thousands</strong></div></th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($) </div>
<div>Investment</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">346<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 811,068<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">52,015<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">863,083<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(3,296)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(145)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (3,441)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">274<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 488,949<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">27,713<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">516,662<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(2,463)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(52)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (2,515)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">30<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 67,854<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">67,854<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(328)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (328)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">38<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 252,926<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">24,173<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">277,099<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(503)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(93)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (596)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">3<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 643<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">129<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">772<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember', window );">Other Municipal Debt Securities [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 696<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">696<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(2)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (2)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for more than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479081/326-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-7<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for 12 months or longer, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-7<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479081/326-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-7<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-7<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of investments in debt securities measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without an allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in unrealized loss position without allowance for credit loss.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479081/326-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-6<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in unrealized loss position, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-6<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>80
<FILENAME>R63.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929075328">
<tr>
<th class="tl" colspan="2" rowspan="1"><div style="width: 200px;"><strong>Fair Value Measurements (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2"><div>Dec. 31, 2024</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 2,056,008<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 1,964,890<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 46,286<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 49,292<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1.75%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.75%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember', window );">Publicly Traded Equity Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 5,263<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 6,301<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">180,445<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">185,424<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,241,716<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2,156,615<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,032,066<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">801,228<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">33,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">208,998<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">334,828<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">806,724<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">807,679<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">7,524<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">21,155<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">696<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Publicly Traded Equity Securities [Member] | Other Current Assets [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="nump">5,263<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,301<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">180,445<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">185,424<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">992,432<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">999,404<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">806,724<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">807,679<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Publicly Traded Equity Securities [Member] | Other Current Assets [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">5,263<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,301<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,249,284<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,157,211<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 1.75% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NotesPayableFairValueDisclosure', window );">Convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">569,300<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">661,100<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NotesPayableFairValueDisclosure', window );">Convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">612,800<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">667,800<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0.125% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NotesPayableFairValueDisclosure', window );">Convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">42,400<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,032,066<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">801,228<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">208,998<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">334,828<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">7,524<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">21,155<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">696<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="fn" style="border-bottom: 0px;"></td>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr><td colspan="8"></td></tr>
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<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Included in cash and cash equivalents in our consolidated balance
            sheets.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Included in short-term investments in our consolidated balance sheets.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">$33.0 million was included in cash and cash equivalents, with the difference included in short-term investments in our consolidated balance sheets.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[4]</td>
<td style="vertical-align: top;" valign="top">Included in other current assets in our consolidated balance sheets.</td>
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<div style="display: none;">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of asset recognized for present right to economic benefit.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 103<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482078/820-10-55-103<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 100<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482078/820-10-55-100<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-1<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of currency on hand as well as demand deposits with banks or financial institutions. Includes other kinds of accounts that have the general characteristics of demand deposits. Also includes short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI), classified as current.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of notes payable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2E<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2E<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(19))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
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<td><strong> Name:</strong></td>
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<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember</td>
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<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember</td>
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<td style="white-space:nowrap;">us-gaap_BalanceSheetLocationAxis=us-gaap_OtherCurrentAssetsMember</td>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>81
<FILENAME>R64.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
<title></title>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367930606912">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Long-Term Obligations (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongtermDebtCurrentAndNoncurrentAbstract', window );"><strong>Long-Term Obligations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Liability related to sale of future royalties</a></td>
<td class="nump">$ 542,212<span></span>
</td>
<td class="nump">$ 513,736<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Lease liabilities</a></td>
<td class="nump">170,869<span></span>
</td>
<td class="nump">178,969<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LoansPayableToBank', window );">Mortgage debt</a></td>
<td class="nump">8,714<span></span>
</td>
<td class="nump">8,859<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherLiabilities', window );">Other obligations</a></td>
<td class="nump">43,425<span></span>
</td>
<td class="nump">33,714<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LongTermObligations', window );">Total</a></td>
<td class="nump">1,958,781<span></span>
</td>
<td class="nump">1,922,943<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LongTermObligationsCurrent', window );">Less: current portion</a></td>
<td class="num">(9,279)<span></span>
</td>
<td class="num">(8,831)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LongTermObligationsNoncurrent', window );">Total Long-Term Obligations</a></td>
<td class="nump">1,949,502<span></span>
</td>
<td class="nump">1,914,112<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongtermDebtCurrentAndNoncurrentAbstract', window );"><strong>Long-Term Obligations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebt', window );">Convertible senior notes</a></td>
<td class="nump">$ 565,026<span></span>
</td>
<td class="nump">$ 562,285<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongtermDebtCurrentAndNoncurrentAbstract', window );"><strong>Long-Term Obligations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebt', window );">Convertible senior notes</a></td>
<td class="nump">$ 628,535<span></span>
</td>
<td class="nump">$ 625,380<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongtermDebtCurrentAndNoncurrentAbstract', window );"><strong>Long-Term Obligations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after accumulated amortization, of the unamortized liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LongTermObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Including the current and noncurrent portions, amount of long-term debt, lease obligations and other obligations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LongTermObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LongTermObligationsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt, lease obligations and other obligations., classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LongTermObligationsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LongTermObligationsNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt, lease obligations and other obligations, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LongTermObligationsNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Including the current and noncurrent portions, carrying amount of debt identified as being convertible into another form of financial instrument (typically the entity's common stock) as of the balance sheet date, which originally required full repayment more than twelve months after issuance or greater than the normal operating cycle of the company.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16)(a)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LoansPayableToBank">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Including the current and noncurrent portions, carrying value as of the balance sheet date of loans from a bank with maturities initially due after one year or beyond the normal operating cycle if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16)(a)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LoansPayableToBank</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongtermDebtCurrentAndNoncurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongtermDebtCurrentAndNoncurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of liabilities classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(15))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(15))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 946<br> -SubTopic 830<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479168/946-830-55-12<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(12)(b)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(12)(b)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 6: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(12)(b)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 7: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(17))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherLiabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<DOCUMENT>
<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<title></title>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367920985072">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Convertible Debt and Call Spread (Details) - USD ($)<br> $ / shares in Units, $ in Thousands, shares in Millions</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="5">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromConvertibleDebt', window );">Proceeds from issuance of convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 575,000<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">44,504<span></span>
</td>
<td class="nump">487,943<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Gain (loss) on early retirement of debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">13,389<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Unamortized debt issuance costs</a></td>
<td class="nump">$ 13,981<span></span>
</td>
<td class="nump">13,981<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,690<span></span>
</td>
<td class="nump">6,330<span></span>
</td>
<td class="nump">5,373<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotesMember', window );">Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,100<span></span>
</td>
<td class="nump">5,900<span></span>
</td>
<td class="nump">$ 5,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 575,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="nump">575,000<span></span>
</td>
<td class="nump">575,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Unamortized debt issuance costs</a></td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Jun. 30,  2028<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="nump">2.30%<span></span>
</td>
<td class="nump">2.30%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="nump">$ 53.73<span></span>
</td>
<td class="nump">$ 53.73<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="nump">10.7<span></span>
</td>
<td class="nump">10.7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange', window );">Percentage of principal amount used as purchase price upon occurrence of fundamental change</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember', window );">1.75% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromConvertibleDebt', window );">Proceeds from issuance of convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 488,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 632,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="nump">$ 632,500<span></span>
</td>
<td class="nump">$ 632,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Unamortized debt issuance costs</a></td>
<td class="nump">$ 4,000<span></span>
</td>
<td class="nump">$ 4,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Apr. 30,  2026<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="nump">0.50%<span></span>
</td>
<td class="nump">0.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="nump">$ 57.84<span></span>
</td>
<td class="nump">$ 57.84<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread', window );">Effective conversion price per share with call spread (in dollars per share)</a></td>
<td class="nump">$ 76.39<span></span>
</td>
<td class="nump">$ 76.39<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="nump">10.9<span></span>
</td>
<td class="nump">10.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CallSpread', window );">Cost of call spread</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">46,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">136,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfWarrants', window );">Proceeds from issuance of warrants</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">89,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange', window );">Percentage of principal amount used as purchase price upon occurrence of fundamental change</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember', window );">0% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromConvertibleDebt', window );">Proceeds from issuance of convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">319,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromConvertibleDebt', window );">Proceeds from issuance of convertible senior notes</a></td>
<td class="nump">$ 44,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 504,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Dec. 31,  2024<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="nump">$ 83.28<span></span>
</td>
<td class="nump">$ 83.28<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread', window );">Effective conversion price per share with call spread (in dollars per share)</a></td>
<td class="nump">$ 123.38<span></span>
</td>
<td class="nump">$ 123.38<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CallSpread', window );">Cost of call spread</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 52,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">108,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfWarrants', window );">Proceeds from issuance of warrants</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">56,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member] | Other Income [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Gain (loss) on early retirement of debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 13,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember', window );">0.125% Notes Issued in Exchange for 1% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">439,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember', window );">0.125% Notes Issued under Subscription Agreements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">109,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 309,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentRepurchasedFaceAmount', window );">Principal amount repurchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 375,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CallSpread">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The net cash outflow from payments for hedge transactions and proceeds from the issuance of warrants. The call spread transaction was entered into to minimize the impact of potential economic dilution upon conversion of the 0.125% notes issued.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CallSpread</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The computed conversion price per share of the debt instrument based on the the conversion feature embedded in the debt instrument and the impact of the purchased hedges in the call spread transaction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of the principal amount of the notes to be purchased, plus accrued and unpaid interest, upon the occurrence of certain fundamental changes, as set forth in the indenture governing the convertible notes.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertibleSharesSubjectToConversion">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of shares of common stock subject to conversion if the debt was converted to equity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertibleSharesSubjectToConversion</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AmortizationOfFinancingCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense attributable to debt issuance costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1F<br> -Subparagraph (b)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1F<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfFinancingCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentCarryingAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before unamortized (discount) premium and debt issuance costs, of long-term debt. Includes, but is not limited to, notes payable, bonds payable, commercial loans, mortgage loans, convertible debt, subordinated debt and other types of debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentCarryingAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentConvertibleConversionPrice1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The price per share of the conversion feature embedded in the debt instrument.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentConvertibleConversionPrice1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face (par) amount of debt instrument at time of issuance.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482949/835-30-55-8<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69B<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481568/470-20-55-69B<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69C<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481568/470-20-55-69C<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482900/835-30-50-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentFaceAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Effective interest rate for the funds borrowed under the debt agreement considering interest compounding and original issue discount or premium.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482949/835-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482900/835-30-50-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateEffectivePercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentMaturityDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Date when the debt instrument is scheduled to be fully repaid, in YYYY-MM-DD format.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentMaturityDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:dateItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentRepurchasedFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face (par) amount of the original debt instrument that was repurchased.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentRepurchasedFaceAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredFinanceCostsNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after accumulated amortization, of debt issuance costs. Includes, but is not limited to, legal, accounting, underwriting, printing, and registration costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-1A<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-2<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482900/835-30-50-1<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1D<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredFinanceCostsNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainsLossesOnExtinguishmentOfDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Difference between the fair value of payments made and the carrying amount of debt which is extinguished prior to maturity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481303/470-50-40-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481303/470-50-40-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainsLossesOnExtinguishmentOfDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsForHedgeFinancingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for a financial contract that meets the hedge criteria as either cash flow hedge, fair value hedge or hedge of net investment in foreign operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 27<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-27<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForHedgeFinancingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the issuance of a long-term debt instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfWarrants">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from issuance of rights to purchase common shares at predetermined price (usually issued together with corporate debt).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfWarrants</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow from the repayment of a long-term debt instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td>na</td>
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<tr>
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<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
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<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeStatementLocationAxis=us-gaap_OtherNonoperatingIncomeExpenseMember</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember</td>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>83
<FILENAME>R66.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<html>
<head>
<title></title>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929257136">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Financing Arrangements (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="4">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Aug. 31, 2023 </div>
<div>USD ($) </div>
<div>Lot</div>
</th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($) </div>
<div>Option</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($) </div>
<div>Facility</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt', window );">Number of purchased facilities financed with mortgage debt | Facility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor', window );">Number of purchase and sale agreements entered into with real estate investor | Agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossOnDispositionOfAssets1', window );">Gain on sale of real estate assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (12)<span></span>
</td>
<td class="num">$ (161)<span></span>
</td>
<td class="nump">$ 149,604<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment', window );">Proceeds from sale of real estate assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">22<span></span>
</td>
<td class="nump">254,083<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfSecuredDebt', window );">Payment of mortgage debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 167<span></span>
</td>
<td class="nump">$ 160<span></span>
</td>
<td class="nump">50,686<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_LongTermMortgageDebtMember', window );">Long-term Mortgage Debt [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 60,400<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_PrimaryResearchAndDevelopmentFacilityMortgageMember', window );">Primary R&amp;D Facility Mortgage [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan', window );">Period to make interest only payments on mortgage loan</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfSecuredDebt', window );">Payment of mortgage debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">51,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ManufacturingFacilityMortgageMember', window );">Manufacturing Facility Mortgage [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan', window );">Period to make interest only payments on mortgage loan</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PrimaryResearchAndDevelopmentFacilityMember', window );">Primary R&amp;D Facility [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireBuildings', window );">Payment to acquire building</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 79,400<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3.88%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_ManufacturingFacilityMember', window );">Manufacturing Facility [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireBuildings', window );">Payment to acquire building</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 14,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4.20%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember', window );">Headquarters Location in Carlsbad, California [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossOnDispositionOfAssets1', window );">Gain on sale of real estate assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor', window );">Number of lots of undeveloped land transferred to real estate investor | Lot</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment', window );">Proceeds from sale of real estate assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 263,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Initial term of lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">15 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember', window );">Undeveloped Land in Carlsbad, California [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor', window );">Number of lots of undeveloped land transferred to real estate investor | Lot</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment', window );">Proceeds from sale of real estate assets</a></td>
<td class="nump">$ 33,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember', window );">New R&amp;D Facility in Carlsbad, CA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Initial term of lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">15 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of options to extend the lease under the lessee's operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of lots of undeveloped land adjacent to the Company's headquarters transferred to real estate investor.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of purchase and sale agreements entered into with a real estate investor.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of purchased facilities financed with mortgage debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period of time to make only payments of interest on the mortgage loan, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face (par) amount of debt instrument at time of issuance.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482949/835-30-55-8<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69B<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481568/470-20-55-69B<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69C<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481568/470-20-55-69C<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482900/835-30-50-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentFaceAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainLossOnDispositionOfAssets1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) on sale or disposal of assets, including but not limited to property plant and equipment, intangible assets and equity in securities of subsidiaries or equity method investee.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainLossOnDispositionOfAssets1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseRenewalTerm">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease renewal, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseRenewalTerm</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseTermOfContract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseTermOfContract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireBuildings">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for acquisition of buildings (properties) whether for investment or use.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-13<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquireBuildings</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the sale of long-lived, physical assets that are used in the normal conduct of business to produce goods and services and not intended for resale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfSecuredDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to repay long-term debt that is wholly or partially secured by collateral. Excludes repayments of tax exempt secured debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfSecuredDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_LongTermMortgageDebtMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_LongTermMortgageDebtMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_PrimaryResearchAndDevelopmentFacilityMortgageMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_PrimaryResearchAndDevelopmentFacilityMortgageMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ManufacturingFacilityMortgageMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ManufacturingFacilityMortgageMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PrimaryResearchAndDevelopmentFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PrimaryResearchAndDevelopmentFacilityMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_ManufacturingFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_ManufacturingFacilityMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931559248">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Debt Maturity Schedules (Details)<br> $ in Thousands</strong></div></th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_MaturitiesOfLongTermDebtAbstract', window );"><strong>Debt Maturities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths', window );">2025</a></td>
<td class="nump">$ 10,657<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo', window );">2026</a></td>
<td class="nump">643,157<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree', window );">2027</a></td>
<td class="nump">18,737<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour', window );">2028</a></td>
<td class="nump">580,091<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive', window );">2029</a></td>
<td class="nump">60<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive', window );">Thereafter</a></td>
<td class="nump">360<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebt', window );">Total debt and mortgage maturities</a></td>
<td class="nump">1,253,062<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtCurrent', window );">Less: Current portion included in other current liabilities</a></td>
<td class="num">(165)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InterestPayableCurrentAndNoncurrent', window );">Less: Fixed and determinable interest</a></td>
<td class="num">(36,511)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Less: Debt issuance costs</a></td>
<td class="num">(13,981)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtNoncurrent', window );">Total debt</a></td>
<td class="nump">$ 1,202,405<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredFinanceCostsNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after accumulated amortization, of debt issuance costs. Includes, but is not limited to, legal, accounting, underwriting, printing, and registration costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-1A<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-2<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482900/835-30-50-1<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1D<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredFinanceCostsNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InterestPayableCurrentAndNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of interest payable on debt, including, but not limited to, trade payables.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(15)(5))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(15)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InterestPayableCurrentAndNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of unamortized premium (discount) and debt issuance cost, of long-term debt. Excludes lease obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482949/835-30-55-8<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69B<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481568/470-20-55-69B<br><br>Reference 5: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69C<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481568/470-20-55-69C<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1D<br><br>Reference 7: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16)(a)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebtCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of unamortized premium (discount) and debt issuance cost, of long-term debt classified as current. Excludes lease obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing after fifth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481544/470-10-50-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1E<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing in next fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1E<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481544/470-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing in fifth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1E<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481544/470-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing in fourth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1E<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481544/470-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing in third fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1E<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481544/470-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing in second fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1E<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481544/470-10-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of unamortized premium (discount) and debt issuance cost, of long-term debt classified as noncurrent. Excludes lease obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MaturitiesOfLongTermDebtAbstract</td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367928265232">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Operating Leases (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Aug. 31, 2023 </div>
<div>Lot</div>
</th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($) </div>
<div>Option</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Lease payments to be made over initial term of lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 260,238<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAsset', window );">Right-of-use operating lease assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">161,856<span></span>
</td>
<td class="nump">$ 171,896<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Operating lease liabilities</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 170,869<span></span>
</td>
<td class="nump">178,969<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1', window );">Weighted average remaining lease term</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">12 years 1 month 6 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent', window );">Weighted average discount rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6.90%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeasePayments', window );">Operating lease cash payments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 20,500<span></span>
</td>
<td class="nump">20,100<span></span>
</td>
<td class="nump">$ 4,000<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadFacilityMember', window );">Carlsbad Facility [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadOfficeSpaceMember', window );">Carlsbad Office Space [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadWarehouseSpaceMember', window );">Carlsbad Warehouse Space [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember', window );">Headquarters Location in Carlsbad, California [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Initial term of lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">15 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Lease payments to be made over initial term of lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 280,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor', window );">Number of lots of undeveloped land transferred to real estate investor | Lot</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember', window );">Development Chemistry and Manufacturing Facility in Oceanside, California [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ImpairmentOfLongLivedAssetsHeldForUse', window );">Impairment charge</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 20,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration', window );">Impairment, Long-Lived Asset, Held-for-Use, Statement of Income [Extensible Enumeration]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Selling, General and Administrative Expense<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_BostonOfficeSpaceMember', window );">Boston Office Space [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Initial term of lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">123 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeasePeriodOfFreeRent', window );">Period of free rent under lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">3 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_SubleasedOfficeSpaceInBostonMember', window );">Subleased Office Space in Boston [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LessorOperatingLeaseTermOfContract', window );">Term of sublease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">83 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LessorOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend sublease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LessorOperatingLeasePeriodOfFreeRent', window );">Period of free rent under sublease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LessorOperatingLeasePaymentsToBeReceived', window );">Lease payments to be received over term of sublease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 9,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_AnotherOfficeSpaceInBostonMember', window );">Another Office Space in Boston [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Initial term of lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">91 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeasePeriodOfFreeRent', window );">Period of free rent under lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Lease payments to be made over initial term of lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 6,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of options to extend the lease under the lessee's operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeasePeriodOfFreeRent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period of time in which the rent is free under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeasePeriodOfFreeRent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LessorOperatingLeaseNumberOfOptionsToExtendLease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of options to extend the lease under the lessor's operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LessorOperatingLeaseNumberOfOptionsToExtendLease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LessorOperatingLeasePeriodOfFreeRent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period of time in which the lessor provides free rent under operating lease to the lessee, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LessorOperatingLeasePeriodOfFreeRent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of lots of undeveloped land adjacent to the Company's headquarters transferred to real estate investor.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicates line item in statement of income or comprehensive income that includes impairment of long-lived asset held for use.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 360<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482099/360-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>enum2:enumerationSetItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ImpairmentOfLongLivedAssetsHeldForUse">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate amount of write-downs for impairments recognized during the period for long lived assets held for use (including those held for disposal by means other than sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 100<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482078/820-10-55-100<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 360<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482099/360-10-50-2<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482130/360-10-45-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ImpairmentOfLongLivedAssetsHeldForUse</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseRenewalTerm">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease renewal, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseRenewalTerm</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseTermOfContract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseTermOfContract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LessorOperatingLeasePaymentsToBeReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lease payments to be received by lessor for operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479773/842-30-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LessorOperatingLeasePaymentsToBeReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LessorOperatingLeaseTermOfContract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of lessor's operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 842<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479773/842-30-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LessorOperatingLeaseTermOfContract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeasePayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow from operating lease, excluding payments to bring another asset to condition and location necessary for its intended use.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 5<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-5<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeasePayments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseRightOfUseAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's right to use underlying asset under operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseRightOfUseAsset</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average discount rate for operating lease calculated at point in time.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 53<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479589/842-20-55-53<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(4)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average remaining lease term for operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 53<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479589/842-20-55-53<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadFacilityMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadOfficeSpaceMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadOfficeSpaceMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadWarehouseSpaceMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadWarehouseSpaceMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_BostonOfficeSpaceMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_BostonOfficeSpaceMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_SubleasedOfficeSpaceInBostonMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_SubleasedOfficeSpaceInBostonMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_AnotherOfficeSpaceInBostonMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931256384">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Future Payments for Operating Lease Liabilities (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract', window );"><strong>Future Payments for Operating Lease Liabilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths', window );">2025</a></td>
<td class="nump">$ 20,870<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo', window );">2026</a></td>
<td class="nump">21,032<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree', window );">2027</a></td>
<td class="nump">21,054<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour', window );">2028</a></td>
<td class="nump">20,973<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive', window );">2029</a></td>
<td class="nump">18,687<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive', window );">Thereafter</a></td>
<td class="nump">157,622<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Total minimum lease payments</a></td>
<td class="nump">260,238<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount', window );">Less: Imputed interest</a></td>
<td class="num">(89,369)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrent', window );">Less: Current portion (included in other current liabilities)</a></td>
<td class="num">(9,064)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityNoncurrent', window );">Total long-term lease liabilities</a></td>
<td class="nump">$ 161,805<span></span>
</td>
<td class="nump">$ 170,875<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList', window );">Operating Lease, Liability, Current, Statement of Financial Position [Extensible Enumeration]</a></td>
<td class="text">Other current liabilities<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseExpense', window );">Rent expense</a></td>
<td class="nump">$ 23,200<span></span>
</td>
<td class="nump">$ 23,100<span></span>
</td>
<td class="nump">$ 8,300<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease due after fifth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease to be paid in next fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease to be paid in fifth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease to be paid in fourth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease to be paid in third fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease to be paid in second fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments in excess of discounted obligation for lease payments for operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of operating lease expense. Excludes sublease income.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 4<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease, classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicates line item in statement of financial position that includes current operating lease liability.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>enum2:enumerationSetItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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</table></div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367921164176">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Royalty Revenue Monetization (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Jan. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontRoyaltyPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones', window );">Maximum amount of payments receivable for additional milestones</a></td>
<td class="nump">625,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Transaction costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 10,434<span></span>
</td>
<td class="nump">$ 29<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ProceedsFromSaleOfFutureRoyalties', window );">Proceeds from sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">500,000<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Issuance costs related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,434)<span></span>
</td>
<td class="num">(29)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPayments', window );">Royalty payments to Royalty Pharma</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(44,981)<span></span>
</td>
<td class="num">(44,628)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_InterestExpenseRelatedToSaleOfFutureRoyalties', window );">Interest expense related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">72,846<span></span>
</td>
<td class="nump">68,238<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Net liability related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">542,212<span></span>
</td>
<td class="nump">513,736<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaMember', window );">SPINRAZA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid', window );">Maximum amount of annual sales on which royalty payments are paid</a></td>
<td class="nump">$ 1,500,000<span></span>
</td>
<td class="nump">$ 1,500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaMember', window );">SPINRAZA [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid on annual sales of medicine</a></td>
<td class="nump">25.00%<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="nump">$ 475,000<span></span>
</td>
<td class="nump">$ 475,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaMember', window );">SPINRAZA [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid on annual sales of medicine</a></td>
<td class="nump">45.00%<span></span>
</td>
<td class="nump">45.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="nump">$ 550,000<span></span>
</td>
<td class="nump">$ 550,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_PelacarsenMember', window );">Pelacarsen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid on annual sales of medicine</a></td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RoyaltyPurchaseAgreementMember', window );">Royalty Purchase Agreement [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Transaction costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,400<span></span>
</td>
<td class="nump">$ 10,434<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">13.50%<span></span>
</td>
<td class="nump">13.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ProceedsFromSaleOfFutureRoyalties', window );">Proceeds from sale of future royalties</a></td>
<td class="nump">$ 500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Issuance costs related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (10,400)<span></span>
</td>
<td class="num">$ (10,434)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPayments', window );">Royalty payments to Royalty Pharma</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(44,981)<span></span>
</td>
<td class="num">(44,628)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_InterestExpenseRelatedToSaleOfFutureRoyalties', window );">Interest expense related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">72,846<span></span>
</td>
<td class="nump">68,238<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties', window );">Amortization of issuance costs related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">611<span></span>
</td>
<td class="nump">560<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Net liability related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 542,212<span></span>
</td>
<td class="nump">$ 513,736<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense attributable to the sale of future royalties.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_InterestExpenseRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of interest expense using the effective interest rate method related to the sale of future royalties.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_InterestExpenseRelatedToSaleOfFutureRoyalties</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after accumulated amortization, of the unamortized liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of annual sales on which royalty payments are paid under the royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for additional milestones under the royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Maximum royalty payments under the royalty purchase agreement made before royalty interest reverts back to the Company.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow paid to third parties for transaction costs in connection with a monetization transaction of future SPINRAZA and pelacarsen royalties the Company is entitled to under collaboration and licensing agreements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of royalty payments paid on annual sales of medicine.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ProceedsFromSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the sale of future royalties under a royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ProceedsFromSaleOfFutureRoyalties</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of royalty payments made during the period under a royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPayments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyRevenueMonetizationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyRevenueMonetizationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontRoyaltyPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontRoyaltyPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Effective interest rate for the funds borrowed under the debt agreement considering interest compounding and original issue discount or premium.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482949/835-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482900/835-30-50-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateEffectivePercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_SpinrazaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_SpinrazaMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
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<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_PelacarsenMember</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_RoyaltyPurchaseAgreementMember</td>
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<DOCUMENT>
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
<title></title>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929233552">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Preferred and Common Stock (Details) - USD ($)<br> $ / shares in Units, $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2024</div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockNumberOfSharesParValueAndOtherDisclosuresAbstract', window );"><strong>Common Stock [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesAuthorized', window );">Common stock, shares authorized to issue (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">300,000,000<span></span>
</td>
<td class="nump">300,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">157,908,815<span></span>
</td>
<td class="nump">144,340,526<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesOutstanding', window );">Common stock, shares outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">157,908,815<span></span>
</td>
<td class="nump">144,340,526<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Net proceeds from stock option exercises, vesting of restricted stock units, and ESPP purchases</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 33,609<span></span>
</td>
<td class="nump">$ 49,442<span></span>
</td>
<td class="nump">$ 6,373<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfCommonStock', window );">Net proceeds</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 489,120<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementClassOfStockAxis=us-gaap_PreferredStockMember', window );">Preferred Stock [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockNumberOfSharesParValueAndOtherDisclosuresAbstract', window );"><strong>Preferred Stock [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockSharesAuthorized', window );">Preferred stock, shares authorized (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockSharesOutstanding', window );">Preferred stock, shares outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementClassOfStockAxis=us-gaap_SeriesCPreferredStockMember', window );">Series C Junior Participating Preferred Stock [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockNumberOfSharesParValueAndOtherDisclosuresAbstract', window );"><strong>Preferred Stock [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockSharesIssued', window );">Preferred stock, shares issued (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockSharesOutstanding', window );">Preferred stock, shares outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementClassOfStockAxis=us-gaap_CommonStockMember', window );">Common Stock [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockNumberOfSharesParValueAndOtherDisclosuresAbstract', window );"><strong>Common Stock [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesAuthorized', window );">Common stock, shares authorized to issue (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">300,000,000<span></span>
</td>
<td class="nump">300,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">157,900,000<span></span>
</td>
<td class="nump">144,300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesOutstanding', window );">Common stock, shares outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">157,900,000<span></span>
</td>
<td class="nump">144,300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance', window );">Common shares reserved for future issuance (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">48,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross', window );">Number of shares issued for stock option exercises, vesting of restricted stock units, and ESPP purchases (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,100,000<span></span>
</td>
<td class="nump">2,300,000<span></span>
</td>
<td class="nump">1,200,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Net proceeds from stock option exercises, vesting of restricted stock units, and ESPP purchases</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 33,600<span></span>
</td>
<td class="nump">$ 49,400<span></span>
</td>
<td class="nump">$ 6,400<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesNewIssues', window );">Issuance of public common stock, net (in shares)</a></td>
<td class="nump">11,500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssuedPricePerShare', window );">Share price (in dollars per share)</a></td>
<td class="nump">$ 43.5<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfCommonStock', window );">Net proceeds</a></td>
<td class="nump">$ 489,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsOfStockIssuanceCosts', window );">Underwriting discounts and commissions and other offering expenses</a></td>
<td class="nump">$ 11,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Aggregate number of common shares reserved for future issuance.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockCapitalSharesReservedForFutureIssuance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockNumberOfSharesParValueAndOtherDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockNumberOfSharesParValueAndOtherDisclosuresAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum number of common shares permitted to be issued by an entity's charter and bylaws.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesAuthorized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total number of common shares of an entity that have been sold or granted to shareholders (includes common shares that were issued, repurchased and remain in the treasury). These shares represent capital invested by the firm's shareholders and owners, and may be all or only a portion of the number of shares authorized. Shares issued include shares outstanding and shares held in the treasury.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares of common stock outstanding. Common stock represent the ownership interest in a corporation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481112/505-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.6-05(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-2<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 6: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(7))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsOfStockIssuanceCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for cost incurred directly with the issuance of an equity security.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsOfStockIssuanceCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PreferredStockNumberOfSharesParValueAndOtherDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PreferredStockNumberOfSharesParValueAndOtherDisclosuresAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PreferredStockSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum number of nonredeemable preferred shares (or preferred stock redeemable solely at the option of the issuer) permitted to be issued by an entity's charter and bylaws.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PreferredStockSharesAuthorized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PreferredStockSharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares issued for nonredeemable preferred shares and preferred shares redeemable solely at option of issuer. Includes, but is not limited to, preferred shares issued, repurchased, and held as treasury shares. Excludes preferred shares classified as debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 13<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481112/505-10-50-13<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PreferredStockSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PreferredStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Aggregate share number for all nonredeemable preferred stock (or preferred stock redeemable solely at the option of the issuer) held by stockholders. Does not include preferred shares that have been repurchased.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.6-05(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-2<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(7))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PreferredStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the additional capital contribution to the entity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfCommonStock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from issuance of shares under share-based payment arrangement. Includes, but is not limited to, option exercised.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-14<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 718<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesIssuedPricePerShare">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Per share or per unit amount of equity securities issued.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesIssuedPricePerShare</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesNewIssues">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of new stock issued during the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481112/505-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 505<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478448/946-505-50-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(i)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479886/946-10-S99-3<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480008/505-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesNewIssues</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number, before forfeiture, of shares issued under share-based payment arrangement. Excludes employee stock ownership plan (ESOP).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
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<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementClassOfStockAxis=us-gaap_PreferredStockMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementClassOfStockAxis=us-gaap_PreferredStockMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementClassOfStockAxis=us-gaap_SeriesCPreferredStockMember</td>
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<td></td>
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<td>na</td>
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<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<td style="white-space:nowrap;">us-gaap_StatementClassOfStockAxis=us-gaap_CommonStockMember</td>
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<td></td>
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<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367919475584">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Stock Plans (Details)<br></strong></div></th>
<th class="th" colspan="12">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>Officer </div>
<div>$ / shares </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2016 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2015 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2014 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2013 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2012 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2011 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2010 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2009 </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2023 </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2021 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2019 </div>
<div>shares</div>
</th>
<th class="th">
<div>May 31, 2017 </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2015 </div>
<div>shares</div>
</th>
<th class="th">
<div>May 31, 2015 </div>
<div>shares</div>
</th>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_StockOptionMember', window );">Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="nump">14,717,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">14,091,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="nump">10,089,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_StockOptionPlan1989Member', window );">1989 Stock Option Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized for issuance under the Plan (in shares)</a></td>
<td class="nump">20,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_StockOptionPlan1989Member', window );">1989 Stock Option Plan [Member] | Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">7 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_StockOptionPlan1989Member', window );">1989 Stock Option Plan [Member] | Stock Options [Member] | One Year from Date of Grant [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1', window );">Period before options are exercisable</a></td>
<td class="text">1 year<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized for issuance under the Plan (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">38,500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">35,200,000<span></span>
</td>
<td class="nump">29,700,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">23,000,000<span></span>
</td>
<td class="nump">16,000,000<span></span>
</td>
<td class="nump">11,000,000<span></span>
</td>
<td class="nump">5,500,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward', window );">Reduction in fungible share reserve for each share issued pursuant to full value award (n shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(1.7)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward', window );">Increase in fungible share reserve for each share returning from a full value award (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="nump">13,300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="nump">9,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="nump">7,300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Number of executive officers terminated before change in control when vesting will accelerate for executive officers | Officer</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Period before change in control when vesting will accelerate for executive officers</a></td>
<td class="text">3 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Period after change in control when vesting will accelerate for executive officers</a></td>
<td class="text">12 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member] | Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">7 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member] | Stock Options [Member] | Issued after December 31, 2021 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member] | Stock Options [Member] | One Year from Date of Grant [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1', window );">Period before options are exercisable</a></td>
<td class="text">1 year<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member] | Restricted Stock Units [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber', window );">Number of awards outstanding (in shares)</a></td>
<td class="nump">3,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized for issuance under the Plan (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,600,000<span></span>
</td>
<td class="nump">2,600,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="nump">500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="nump">200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="nump">800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member] | Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">7 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member] | Stock Options [Member] | Issued after December 31, 2021 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member] | Stock Options [Member] | One Year from Date of Grant [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1', window );">Period before options are exercisable</a></td>
<td class="text">1 year<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member] | Restricted Stock Units [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber', window );">Number of awards outstanding (in shares)</a></td>
<td class="nump">200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_NonemployeeDirectorsStockOptionPlan2002Member', window );">2002 Non-Employee Directors' Stock Option Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized for issuance under the Plan (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,000,000<span></span>
</td>
<td class="nump">1,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="nump">900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="nump">800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="nump">400,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_NonemployeeDirectorsStockOptionPlan2002Member', window );">2002 Non-Employee Directors' Stock Option Plan [Member] | Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_NonemployeeDirectorsStockOptionPlan2002Member', window );">2002 Non-Employee Directors' Stock Option Plan [Member] | Restricted Stock Units [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber', window );">Number of awards outstanding (in shares)</a></td>
<td class="nump">52,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EmployeeStockPurchasePlanMember', window );">Employee Stock Purchase Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized for issuance under the Plan (in shares)</a></td>
<td class="nump">3,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized', window );">Number of additional shares reserved for issuance (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate', window );">Maximum percentage of employee compensation used to purchase shares</a></td>
<td class="nump">10.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent', window );">Percentage of fair market value used to determine purchase price of stock</a></td>
<td class="nump">85.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod', window );">Holding period for purchased stock</a></td>
<td class="text">6 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans', window );">Shares purchased and issued under ESPP (in shares)</a></td>
<td class="nump">100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased', window );">Weighted average purchase price (in dollars per share) | $ / shares</a></td>
<td class="nump">$ 35.93<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EmployeeStockPurchasePlanSharesAvailableForPurchase', window );">Shares available for purchase under ESPP (in shares)</a></td>
<td class="nump">300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EmployeeStockPurchasePlanSharesAvailableForPurchase">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of shares available for purchase under an employee stock purchase plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EmployeeStockPurchasePlanSharesAvailableForPurchase</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average sales price of shares purchased through an employee stock purchase plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Increase (decrease) in the number of shares in the "fungible" share reserve for each share issued pursuant to full value award.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Increase (decrease) in the number of shares in the "fungible" share reserve for each share of common stock returning from a full value award.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of executive officers terminated by the Company during the period that begins three months before and ends twelve months following a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period of time after a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period of time before a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Represents the holding period from the date of purchase for stock purchased under the plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Estimated period over which an employee is required to provide service in exchange for the equity-based payment award, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period over which grantee's right to exercise award under share-based payment arrangement is no longer contingent on satisfaction of service or performance condition, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days. Includes, but is not limited to, combination of market, performance or service condition.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The highest percentage of annual salary that an employee is permitted to utilize with respect to the plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of equity instruments other than options outstanding, including both vested and non-vested instruments.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of additional shares authorized for issuance under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares authorized for issuance under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The difference between the maximum number of shares (or other type of equity) authorized for issuance under the plan (including the effects of amendments and adjustments), and the sum of: 1) the number of shares (or other type of equity) already issued upon exercise of options or other equity-based awards under the plan; and 2) shares (or other type of equity) reserved for issuance on granting of outstanding awards, net of cancellations and forfeitures, if applicable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of shares into which fully or partially vested stock options outstanding as of the balance sheet date can be currently converted under the option plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of options outstanding, including both vested and non-vested options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of vesting of award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period from grant date that an equity-based award expires, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Purchase price of common stock expressed as a percentage of its fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares issued during the period as a result of an employee stock purchase plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481112/505-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480008/505-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_StockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_StockOptionMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PlanNameAxis=ions_StockOptionPlan1989Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_StockOptionPlan1989Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheOneMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheOneMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardDateAxis=ions_IssuedAfterDecember312021Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_IssuedAfterDecember312021Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PlanNameAxis=ions_NonemployeeDirectorsStockOptionPlan2002Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_NonemployeeDirectorsStockOptionPlan2002Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PlanNameAxis=ions_EmployeeStockPurchasePlanMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_EmployeeStockPurchasePlanMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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</div>
</body>
</html>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>90
<FILENAME>R73.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931601904">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Stock Option Activity (Details) - Stock Options [Member] - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward', window );"><strong>Number of Shares [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Outstanding at beginning of period (in shares)</a></td>
<td class="nump">14,091<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross', window );">Granted (in shares)</a></td>
<td class="nump">2,729<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised', window );">Exercised (in shares)</a></td>
<td class="num">(399)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod', window );">Cancelled/forfeited/expired (in shares)</a></td>
<td class="num">(1,704)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Outstanding at end of period (in shares)</a></td>
<td class="nump">14,717<span></span>
</td>
<td class="nump">14,091<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Exercisable at end of period (in shares)</a></td>
<td class="nump">10,089<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward', window );"><strong>Weighted Average Exercise Price Per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice', window );">Outstanding at beginning of period (in dollars per share)</a></td>
<td class="nump">$ 48.43<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice', window );">Granted (in dollars per share)</a></td>
<td class="nump">49.77<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice', window );">Exercised (in dollars per share)</a></td>
<td class="nump">39.55<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice', window );">Cancelled/forfeited/expired (in dollars per share)</a></td>
<td class="nump">54.4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice', window );">Outstanding at end of period (in dollars per share)</a></td>
<td class="nump">48.23<span></span>
</td>
<td class="nump">$ 48.43<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice', window );">Exercisable at end of period (in dollars per share)</a></td>
<td class="nump">$ 49.85<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract', window );"><strong>Average Remaining Contractual Term, Aggregate Intrinsic Value and Other [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2', window );">Average remaining contractual term, outstanding at end of period</a></td>
<td class="text">5 years 3 months 7 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1', window );">Average remaining contractual term, exercisable at end of period</a></td>
<td class="text">3 years 7 months 28 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue', window );">Aggregate intrinsic value, outstanding at end of period</a></td>
<td class="nump">$ 4,692<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1', window );">Aggregate intrinsic value, exercisable at end of period</a></td>
<td class="nump">$ 3,460<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted average fair value of options granted (in dollars per share)</a></td>
<td class="nump">$ 24.37<span></span>
</td>
<td class="nump">$ 19.72<span></span>
</td>
<td class="nump">$ 18.66<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue', window );">Intrinsic value of options exercised</a></td>
<td class="nump">$ 3,600<span></span>
</td>
<td class="nump">$ 6,000<span></span>
</td>
<td class="nump">$ 1,400<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromStockOptionsExercised', window );">Cash received from exercise of stock options</a></td>
<td class="nump">$ 15,800<span></span>
</td>
<td class="nump">$ 65,100<span></span>
</td>
<td class="nump">$ 3,600<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue', window );">Weighted-average fair value of options exercised (in dollars per share)</a></td>
<td class="nump">$ 48.59<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions', window );">Unrecognized compensation cost related to non-vested stock options</a></td>
<td class="nump">$ 43,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">1 year 1 month 6 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average grant-date fair value of options exercised during the reporting period as calculated by applying the disclosed option pricing methodology.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted-average period over which cost not yet recognized is expected to be recognized for award under share-based payment arrangement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost to be recognized for option under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromStockOptionsExercised">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from exercise of option under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-14<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 718<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromStockOptionsExercised</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of shares into which fully or partially vested stock options outstanding as of the balance sheet date can be currently converted under the option plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted-average price as of the balance sheet date at which grantees can acquire the shares reserved for issuance on vested portions of options outstanding and currently exercisable under the stock option plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated difference between fair value of underlying shares on dates of exercise and exercise price on options exercised (or share units converted) into shares.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For presentations that combine terminations, the number of shares under options that were cancelled during the reporting period as a result of occurrence of a terminating event specified in contractual agreements pertaining to the stock option plan or that expired.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Gross number of share options (or share units) granted during the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average grant-date fair value of options granted during the reporting period as calculated by applying the disclosed option pricing methodology.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount by which the current fair value of the underlying stock exceeds the exercise price of options outstanding.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of options outstanding, including both vested and non-vested options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average price at which grantees can acquire the shares reserved for issuance under the stock option plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average price at which option holders acquired shares when converting their stock options into shares.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average price at which grantees could have acquired the underlying shares with respect to stock options that were terminated.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(03)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average per share amount at which grantees can acquire shares of common stock by exercise of options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of difference between fair value of the underlying shares reserved for issuance and exercise price of vested portions of options outstanding and currently exercisable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average remaining contractual term for vested portions of options outstanding and currently exercisable or convertible, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average remaining contractual term for option awards outstanding, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 718<br> -SubTopic 10<br> -Subparagraph (e)(1)<br> -Name Accounting Standards Codification<br> -Paragraph 2<br> -Section 50<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of share options (or share units) exercised during the current period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481112/505-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480008/505-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_StockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_StockOptionMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<title></title>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367925860176">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Restricted Stock Unit Activity (Details) - Restricted Stock Units [Member] - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Millions</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward', window );"><strong>Number of Shares [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at beginning of period (in shares)</a></td>
<td class="nump">3,239<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod', window );">Granted (in shares)</a></td>
<td class="nump">2,005<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod', window );">Vested (in shares)</a></td>
<td class="num">(1,185)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod', window );">Cancelled/forfeited (in shares)</a></td>
<td class="num">(228)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at end of period (in shares)</a></td>
<td class="nump">3,831<span></span>
</td>
<td class="nump">3,239<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward', window );"><strong>Weighted Average Grant Date Fair Value per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue', window );">Non-vested at beginning of period (in dollars per share)</a></td>
<td class="nump">$ 43.4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Granted (in dollars per share)</a></td>
<td class="nump">50.92<span></span>
</td>
<td class="nump">$ 40.51<span></span>
</td>
<td class="nump">$ 36.14<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue', window );">Vested (in dollars per share)</a></td>
<td class="nump">46.88<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue', window );">Cancelled/forfeited (in dollars per share)</a></td>
<td class="nump">46.83<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue', window );">Non-vested at end of period (in dollars per share)</a></td>
<td class="nump">$ 46.06<span></span>
</td>
<td class="nump">$ 43.4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested units</a></td>
<td class="nump">$ 72.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">1 year 3 months 18 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted-average period over which cost not yet recognized is expected to be recognized for award under share-based payment arrangement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost to be recognized for nonvested award under share-based payment arrangement. Excludes share and unit options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of equity-based payment instruments, excluding stock (or unit) options, that were forfeited during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(03)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average fair value as of the grant date of equity-based award plans other than stock (unit) option plans that were not exercised or put into effect as a result of the occurrence of a terminating event.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(03)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of grants made during the period on other than stock (or unit) option plans (for example, phantom stock or unit plan, stock or unit appreciation rights plan, performance target plan).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average fair value at grant date for nonvested equity-based awards issued during the period on other than stock (or unit) option plans (for example, phantom stock or unit plan, stock or unit appreciation rights plan, performance target plan).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of non-vested equity-based payment instruments, excluding stock (or unit) options, that validly exist and are outstanding as of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Per share or unit weighted-average fair value of nonvested award under share-based payment arrangement. Excludes share and unit options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of equity-based payment instruments, excluding stock (or unit) options, that vested during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average fair value as of grant date pertaining to an equity-based award plan other than a stock (or unit) option plan for which the grantee gained the right during the reporting period, by satisfying service and performance requirements, to receive or retain shares or units, other instruments, or cash in accordance with the terms of the arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367931472128">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Performance Restricted Stock Unit Activity (Details) - Performance Restricted Stock Units [Member] - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Millions</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward', window );"><strong>Number of Shares [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at beginning of period (in shares)</a></td>
<td class="nump">226<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod', window );">Granted (in shares)</a></td>
<td class="nump">179<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod', window );">Vested (in shares)</a></td>
<td class="num">(73)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod', window );">Cancelled/forfeited (in shares)</a></td>
<td class="num">(25)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at end of period (in shares)</a></td>
<td class="nump">307<span></span>
</td>
<td class="nump">226<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward', window );"><strong>Weighted Average Grant Date Fair Value per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue', window );">Non-vested at beginning of period (in dollars per share)</a></td>
<td class="nump">$ 56.04<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Granted (in dollars per share)</a></td>
<td class="nump">78.41<span></span>
</td>
<td class="nump">$ 57.43<span></span>
</td>
<td class="nump">$ 42.28<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue', window );">Vested (in dollars per share)</a></td>
<td class="nump">53.35<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue', window );">Cancelled/forfeited (in dollars per share)</a></td>
<td class="nump">68.21<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue', window );">Non-vested at end of period (in dollars per share)</a></td>
<td class="nump">$ 66.72<span></span>
</td>
<td class="nump">$ 56.04<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested units</a></td>
<td class="nump">$ 10.4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">1 year 4 months 24 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted-average period over which cost not yet recognized is expected to be recognized for award under share-based payment arrangement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost to be recognized for nonvested award under share-based payment arrangement. Excludes share and unit options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of equity-based payment instruments, excluding stock (or unit) options, that were forfeited during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(03)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average fair value as of the grant date of equity-based award plans other than stock (unit) option plans that were not exercised or put into effect as a result of the occurrence of a terminating event.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(03)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of grants made during the period on other than stock (or unit) option plans (for example, phantom stock or unit plan, stock or unit appreciation rights plan, performance target plan).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average fair value at grant date for nonvested equity-based awards issued during the period on other than stock (or unit) option plans (for example, phantom stock or unit plan, stock or unit appreciation rights plan, performance target plan).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of non-vested equity-based payment instruments, excluding stock (or unit) options, that validly exist and are outstanding as of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Per share or unit weighted-average fair value of nonvested award under share-based payment arrangement. Excludes share and unit options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of equity-based payment instruments, excluding stock (or unit) options, that vested during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average fair value as of grant date pertaining to an equity-based award plan other than a stock (or unit) option plan for which the grantee gained the right during the reporting period, by satisfying service and performance requirements, to receive or retain shares or units, other instruments, or cash in accordance with the terms of the arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
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<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367926809984">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Stock-based Compensation Expense (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense, net of amounts capitalized</a></td>
<td class="nump">$ 130,200<span></span>
</td>
<td class="nump">$ 105,809<span></span>
</td>
<td class="nump">$ 100,264<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount', window );">Capitalized stock-based compensation expense</a></td>
<td class="nump">799<span></span>
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<td class="nump">0<span></span>
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<td class="nump">0<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1', window );">Total stock-based compensation expense</a></td>
<td class="nump">130,999<span></span>
</td>
<td class="nump">105,809<span></span>
</td>
<td class="nump">100,264<span></span>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember', window );">Cost of Sales [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense, net of amounts capitalized</a></td>
<td class="nump">767<span></span>
</td>
<td class="nump">499<span></span>
</td>
<td class="nump">533<span></span>
</td>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentMember', window );">Research, Development and Patent [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense, net of amounts capitalized</a></td>
<td class="nump">92,403<span></span>
</td>
<td class="nump">77,826<span></span>
</td>
<td class="nump">73,704<span></span>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember', window );">Selling, General and Administrative [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense, net of amounts capitalized</a></td>
<td class="nump">$ 37,030<span></span>
</td>
<td class="nump">$ 27,484<span></span>
</td>
<td class="nump">$ 26,027<span></span>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AllocatedShareBasedCompensationExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of expense for award under share-based payment arrangement. Excludes amount capitalized.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.F)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479830/718-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (h)(1)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AllocatedShareBasedCompensationExpense</td>
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<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td>duration</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost capitalized for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (h)(1)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
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<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationAbstract">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost expensed and capitalized for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (h)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember</td>
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<DOCUMENT>
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367927854672">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Stock-based Valuation Information (Details)<br></strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">4.10%<span></span>
</td>
<td class="nump">3.80%<span></span>
</td>
<td class="nump">2.10%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">43.70%<span></span>
</td>
<td class="nump">46.80%<span></span>
</td>
<td class="nump">54.50%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">6 years 3 months 18 days<span></span>
</td>
<td class="text">6 years 3 months 18 days<span></span>
</td>
<td class="text">6 years 3 months 18 days<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member] | 2011 Equity Incentive Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">7 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member] | 2011 Equity Incentive Plan [Member] | Issued after December 31, 2021 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member] | 2020 Equity Incentive Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">7 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member] | 2020 Equity Incentive Plan [Member] | Issued after December 31, 2021 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=ions_BoardOfDirectorStockOptionMember', window );">Board of Director Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">4.50%<span></span>
</td>
<td class="nump">3.80%<span></span>
</td>
<td class="nump">2.90%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">49.80%<span></span>
</td>
<td class="nump">52.70%<span></span>
</td>
<td class="nump">56.20%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">7 years 6 months<span></span>
</td>
<td class="text">7 years 8 months 12 days<span></span>
</td>
<td class="text">7 years 4 months 24 days<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockMember', window );">ESPP [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">5.20%<span></span>
</td>
<td class="nump">5.30%<span></span>
</td>
<td class="nump">1.20%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">37.80%<span></span>
</td>
<td class="nump">36.00%<span></span>
</td>
<td class="nump">50.10%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">6 months<span></span>
</td>
<td class="text">6 months<span></span>
</td>
<td class="text">6 months<span></span>
</td>
</tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The estimated dividend rate (a percentage of the share price) to be paid (expected dividends) to holders of the underlying shares over the option's term.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The risk-free interest rate assumption that is used in valuing an option on its own shares.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iv)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
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<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Rate of weighted-average expected volatility for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period from grant date that an equity-based award expires, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Expected term of award under share-based payment arrangement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367933585088">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Loss Before Income Taxes (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxDisclosureAbstract', window );"><strong>Income Taxes [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="num">$ (460,712)<span></span>
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<td class="num">$ (334,707)<span></span>
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<td class="num">$ (258,493)<span></span>
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<td class="nump">644<span></span>
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<td class="nump">742<span></span>
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<td class="nump">508<span></span>
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<td class="num">$ (460,068)<span></span>
</td>
<td class="num">$ (333,965)<span></span>
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<td class="num">$ (257,985)<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of earnings or loss from continuing operations before income taxes that is attributable to domestic operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 10A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-10A<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations, including income (loss) from equity method investments, before deduction of income tax expense (benefit), and income (loss) attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 48<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-48<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 6: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(11))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 9: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 31<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-31<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 235<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477314/942-235-S99-1<br><br>Reference 11: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(10))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 12: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(15))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478524/942-220-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of earnings or loss from continuing operations before income taxes that is attributable to foreign operations, which is defined as Income or Loss generated from operations located outside the entity's country of domicile.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 10A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-10A<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxDisclosureAbstract">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxDisclosureAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367926693152">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Income Tax Expense (Benefit) (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract', window );"><strong>Current [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CurrentFederalTaxExpenseBenefit', window );">Federal</a></td>
<td class="num">$ (5,492)<span></span>
</td>
<td class="nump">$ 35,861<span></span>
</td>
<td class="nump">$ 10,522<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CurrentStateAndLocalTaxExpenseBenefit', window );">State</a></td>
<td class="num">(848)<span></span>
</td>
<td class="num">(3,687)<span></span>
</td>
<td class="nump">1,129<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CurrentForeignTaxExpenseBenefit', window );">Foreign</a></td>
<td class="nump">169<span></span>
</td>
<td class="nump">147<span></span>
</td>
<td class="nump">86<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CurrentIncomeTaxExpenseBenefit', window );">Total current income tax expense (benefit)</a></td>
<td class="num">(6,171)<span></span>
</td>
<td class="nump">32,321<span></span>
</td>
<td class="nump">11,737<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract', window );"><strong>Deferred [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFederalIncomeTaxExpenseBenefit', window );">Federal</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit', window );">State</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredIncomeTaxExpenseBenefit', window );">Total deferred income tax benefit</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Total income tax expense (benefit)</a></td>
<td class="num">$ (6,171)<span></span>
</td>
<td class="nump">$ 32,321<span></span>
</td>
<td class="nump">$ 11,737<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CurrentFederalTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current federal tax expense (benefit) attributable to income (loss) from continuing operations. Includes, but is not limited to, current national tax expense (benefit) for non-US (United States of America) jurisdiction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-9<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentFederalTaxExpenseBenefit</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CurrentForeignTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current foreign income tax expense (benefit) pertaining to income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-9<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentForeignTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CurrentIncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current income tax expense (benefit) pertaining to taxable income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-9<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentIncomeTaxExpenseBenefit</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CurrentStateAndLocalTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current state and local tax expense (benefit) attributable to income (loss) from continuing operations. Includes, but is not limited to, current regional, territorial, and provincial tax expense (benefit) for non-US (United States of America) jurisdiction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-9<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentStateAndLocalTaxExpenseBenefit</td>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredFederalIncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred federal tax expense (benefit) attributable to income (loss) from continuing operations. Includes, but is not limited to, deferred national tax expense (benefit) for non-US (United States of America) jurisdiction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-9<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred income tax expense (benefit) pertaining to income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-9<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredIncomeTaxExpenseBenefit</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred state and local tax expense (benefit) attributable to income (loss) from continuing operations. Includes, but is not limited to, deferred regional, territorial, and provincial tax expense (benefit) for non-US (United States of America) jurisdiction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-9<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-9<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-8<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-10<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -SubTopic 20<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482659/740-20-45-2<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -SubTopic 10<br> -Topic 235<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxExpenseBenefit</td>
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<td>xbrli:monetaryItemType</td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367929124144">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Reconciliation of Statutory to Effective Tax Rate (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationAbstract', window );"><strong>Reconciliation Between Effective and Statutory Tax Rate [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest', window );">Pre-tax loss</a></td>
<td class="num">$ (460,068)<span></span>
</td>
<td class="num">$ (333,965)<span></span>
</td>
<td class="num">$ (257,985)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate', window );">Statutory rate</a></td>
<td class="num">(96,614)<span></span>
</td>
<td class="num">(70,133)<span></span>
</td>
<td class="num">(54,177)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes', window );">State income tax net of federal benefit</a></td>
<td class="num">(11,889)<span></span>
</td>
<td class="num">(22,597)<span></span>
</td>
<td class="num">(13,622)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationForeignIncomeTaxRateDifferential', window );">Foreign</a></td>
<td class="nump">15<span></span>
</td>
<td class="num">(22)<span></span>
</td>
<td class="num">(49)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance', window );">Net change in valuation allowance</a></td>
<td class="nump">152,590<span></span>
</td>
<td class="nump">175,388<span></span>
</td>
<td class="nump">104,951<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationTaxCredits', window );">Tax credits</a></td>
<td class="num">(53,497)<span></span>
</td>
<td class="num">(67,131)<span></span>
</td>
<td class="num">(39,729)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationChangeInEnactedTaxRate', window );">Tax rate change</a></td>
<td class="nump">10,815<span></span>
</td>
<td class="nump">1,023<span></span>
</td>
<td class="num">(3,091)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount', window );">Non-deductible compensation</a></td>
<td class="nump">1,895<span></span>
</td>
<td class="nump">3,814<span></span>
</td>
<td class="nump">3,023<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationNondeductibleExpenseOther', window );">Other non-deductible items</a></td>
<td class="nump">188<span></span>
</td>
<td class="nump">327<span></span>
</td>
<td class="nump">57<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount', window );">Foreign-derived intangible income benefit</a></td>
<td class="num">(21,071)<span></span>
</td>
<td class="num">(7,493)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost', window );">Stock-based compensation</a></td>
<td class="nump">10,732<span></span>
</td>
<td class="nump">19,546<span></span>
</td>
<td class="nump">14,030<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationOtherAdjustments', window );">Other</a></td>
<td class="nump">665<span></span>
</td>
<td class="num">(401)<span></span>
</td>
<td class="nump">344<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Total income tax expense (benefit)</a></td>
<td class="num">$ (6,171)<span></span>
</td>
<td class="nump">$ 32,321<span></span>
</td>
<td class="nump">$ 11,737<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract', window );"><strong>Reconciliation Between Effective and Statutory Tax Rate Percentage [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate', window );">Statutory rate</a></td>
<td class="nump">21.00%<span></span>
</td>
<td class="nump">21.00%<span></span>
</td>
<td class="nump">21.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes', window );">State income tax net of federal benefit</a></td>
<td class="nump">2.60%<span></span>
</td>
<td class="nump">6.80%<span></span>
</td>
<td class="nump">5.30%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential', window );">Foreign</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance', window );">Net change in valuation allowance</a></td>
<td class="num">(33.20%)<span></span>
</td>
<td class="num">(52.50%)<span></span>
</td>
<td class="num">(40.70%)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits', window );">Tax credits</a></td>
<td class="nump">11.60%<span></span>
</td>
<td class="nump">20.10%<span></span>
</td>
<td class="nump">15.40%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationChangeInEnactedTaxRate', window );">Tax rate change</a></td>
<td class="num">(2.40%)<span></span>
</td>
<td class="num">(0.30%)<span></span>
</td>
<td class="nump">1.20%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent', window );">Non-deductible compensation</a></td>
<td class="num">(0.40%)<span></span>
</td>
<td class="num">(1.10%)<span></span>
</td>
<td class="num">(1.20%)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseOther', window );">Other non-deductible items</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="num">(0.10%)<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent', window );">Foreign-derived intangible income benefit</a></td>
<td class="nump">4.60%<span></span>
</td>
<td class="nump">2.20%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost', window );">Stock-based compensation</a></td>
<td class="num">(2.30%)<span></span>
</td>
<td class="num">(5.90%)<span></span>
</td>
<td class="num">(5.40%)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments', window );">Other</a></td>
<td class="num">(0.20%)<span></span>
</td>
<td class="nump">0.10%<span></span>
</td>
<td class="num">(0.10%)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateContinuingOperations', window );">Effective rate</a></td>
<td class="nump">1.30%<span></span>
</td>
<td class="num">(9.70%)<span></span>
</td>
<td class="num">(4.50%)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to compensation in excess of $1 million paid to any "covered employee" of the corporation under Section 162(m) of the Tax Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to compensation in excess of $1 million paid to any "covered employee" of the corporation under Section 162(m) of the Tax Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateContinuingOperations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateContinuingOperations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of domestic federal statutory tax rate applicable to pretax income (loss).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.1.Q1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to changes in the valuation allowance for deferred tax assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (a)(6)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationChangeInEnactedTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to changes in the income tax rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationChangeInEnactedTaxRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of reported income tax benefit from difference to expected income tax expense (benefit) computed by applying domestic federal statutory income tax rate to pretax income (loss) from continuing operations, attributable to foreign-derived intangible income (FDII).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (b)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of reported income tax benefit from difference to income tax expense (benefit) computed by applying domestic federal statutory income tax rate to pretax income (loss) from continuing operations, attributable to foreign-derived intangible income (FDII).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (b)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations applicable to statutory income tax expense (benefit) outside of the country of domicile.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Subparagraph (b)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to other nondeductible expenses.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (b)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseOther</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying domestic federal statutory income tax rate to pretax income (loss) from continuing operation, attributable to nondeductible expense for share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (b)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to other adjustments.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Subparagraph (b)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations applicable to state and local income tax expense (benefit), net of federal tax expense (benefit).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to tax credits. Including, but not limited to, research credit, foreign tax credit, investment tax credit, and other tax credits.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (b)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (a)(5)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations, including income (loss) from equity method investments, before deduction of income tax expense (benefit), and income (loss) attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 48<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-48<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 6: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(11))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 9: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 31<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-31<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 235<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477314/942-235-S99-1<br><br>Reference 11: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(10))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 12: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(15))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478524/942-220-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-9<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-8<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-10<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -SubTopic 20<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482659/740-20-45-2<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -SubTopic 10<br> -Topic 235<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to increase (decrease) in the valuation allowance for deferred tax assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (a)(6)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationChangeInEnactedTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations, attributable to increase (decrease) in the income tax rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482525/740-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationChangeInEnactedTaxRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationForeignIncomeTaxRateDifferential">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to foreign income tax expense (benefit).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Subparagraph (b)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationForeignIncomeTaxRateDifferential</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of income tax expense or benefit for the period computed by applying the domestic federal statutory tax rates to pretax income from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationNondeductibleExpenseOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to other nondeductible expenses.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (b)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationNondeductibleExpenseOther</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of reported income tax expense (benefit) in excess of (less than) expected income tax expense (benefit) computed by applying domestic federal statutory income tax rate to pretax income (loss) from continuing operation, attributable to nondeductible expense for award under share-based payment arrangement. Includes, but is not limited to, expense determined to be nondeductible upon grant or after for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (b)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationOtherAdjustments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to other adjustments.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Subparagraph (b)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationOtherAdjustments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to state and local income tax expense (benefit).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationTaxCredits">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to tax credits. Including, but not limited to, research credit, foreign tax credit, investment tax credit, and other tax credits.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (b)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12A<br> -Subparagraph (a)(5)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12A<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationTaxCredits</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367930853808">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Deferred Tax Assets and Liabilities (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsGrossAbstract', window );"><strong>Deferred Tax Assets [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsOperatingLossCarryforwards', window );">Net operating loss carryovers</a></td>
<td class="nump">$ 95,851<span></span>
</td>
<td class="nump">$ 77,964<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsTaxCreditCarryforwards', window );">Tax credits</a></td>
<td class="nump">310,703<span></span>
</td>
<td class="nump">239,962<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsDeferredIncome', window );">Deferred revenue</a></td>
<td class="nump">54,063<span></span>
</td>
<td class="nump">71,683<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost', window );">Stock-based compensation</a></td>
<td class="nump">82,660<span></span>
</td>
<td class="nump">77,468<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets', window );">Intangible and capital assets</a></td>
<td class="nump">93,541<span></span>
</td>
<td class="nump">104,380<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DeferredTaxAssetsFinancingArrangements', window );">Convertible debt</a></td>
<td class="nump">9,310<span></span>
</td>
<td class="nump">16,849<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses', window );">Capitalized research and development expenses</a></td>
<td class="nump">323,560<span></span>
</td>
<td class="nump">238,738<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DeferredTaxAssetsLeasingArrangements', window );">Long-term lease liabilities</a></td>
<td class="nump">41,481<span></span>
</td>
<td class="nump">43,718<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DeferredTaxAssetsSaleOfFutureRoyalties', window );">Sale of future royalties</a></td>
<td class="nump">148,918<span></span>
</td>
<td class="nump">144,608<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsOther', window );">Other</a></td>
<td class="nump">14,024<span></span>
</td>
<td class="nump">10,343<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsGross', window );">Total deferred tax assets</a></td>
<td class="nump">1,174,111<span></span>
</td>
<td class="nump">1,025,713<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxLiabilitiesAbstract', window );"><strong>Deferred Tax Liabilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment', window );">Fixed assets</a></td>
<td class="num">(5,719)<span></span>
</td>
<td class="num">(4,166)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxLiabilitiesLeasingArrangements', window );">Right-of-use assets</a></td>
<td class="num">(36,788)<span></span>
</td>
<td class="num">(42,007)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxLiabilitiesOther', window );">Other</a></td>
<td class="num">(1,896)<span></span>
</td>
<td class="num">(1,910)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance', window );">Net deferred tax asset</a></td>
<td class="nump">1,129,708<span></span>
</td>
<td class="nump">977,630<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsValuationAllowance', window );">Valuation allowance</a></td>
<td class="num">(1,129,708)<span></span>
</td>
<td class="num">(977,630)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsLiabilitiesNet', window );">Total net deferred tax assets and liabilities</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease', window );">Increase in valuation allowance</a></td>
<td class="nump">$ 152,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to capitalized research and development expenses.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DeferredTaxAssetsFinancingArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from financing arrangements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DeferredTaxAssetsFinancingArrangements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DeferredTaxAssetsLeasingArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to leasing arrangements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DeferredTaxAssetsLeasingArrangements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Represents the net amount of deferred tax assets (before reduction for valuation allowance) and liabilities as of the balance sheet date, which result from applying the applicable enacted tax rate to net temporary differences and carryforwards pertaining to assets or liabilities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DeferredTaxAssetsSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to the sale of future royalties.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DeferredTaxAssetsSaleOfFutureRoyalties</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsDeferredIncome">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from deferred income.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsDeferredIncome</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from intangible assets including goodwill.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences and carryforwards.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsGross</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsGrossAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsGrossAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsLiabilitiesNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after allocation of valuation allowances and deferred tax liability, of deferred tax asset attributable to deductible differences and carryforwards, without jurisdictional netting.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsLiabilitiesNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsOperatingLossCarryforwards">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible operating loss carryforwards.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsOperatingLossCarryforwards</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before allocation of valuation allowance, of deferred tax asset attributable to deductible temporary differences, classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsOther</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsTaxCreditCarryforwards">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before allocation of a valuation allowances, of deferred tax assets attributable to deductible tax credit carryforwards including, but not limited to, research, foreign, general business, alternative minimum tax, and other deductible tax credit carryforwards.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsTaxCreditCarryforwards</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from share-based compensation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsValuationAllowance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred tax assets for which it is more likely than not that a tax benefit will not be realized.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsValuationAllowance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxLiabilitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxLiabilitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxLiabilitiesLeasingArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred tax liability attributable to taxable temporary differences from leasing arrangements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxLiabilitiesLeasingArrangements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxLiabilitiesOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred tax liability attributable to taxable temporary differences classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxLiabilitiesOther</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred tax liability attributable to taxable temporary differences from property, plant, and equipment.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in valuation and qualifying accounts and reserves.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 4<br> -Subparagraph (SX 210.12-09)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367930458096">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Income Taxes, Tax Credit Carryforwards (Details)<br> $ in Millions</strong></div></th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardAxis=us-gaap_ResearchMember', window );">Research and Development [Member] | Federal [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardLineItems', window );"><strong>Tax Credit Carryforwards [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardAmount', window );">Tax credit carryforwards</a></td>
<td class="nump">$ 234.2<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardAxis=us-gaap_ResearchMember', window );">Research and Development [Member] | California [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardLineItems', window );"><strong>Tax Credit Carryforwards [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardAmount', window );">Tax credit carryforwards</a></td>
<td class="nump">137.6<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxAuthorityAxis=us-gaap_DomesticCountryMember', window );">Federal [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLossCarryforwardsLineItems', window );"><strong>Operating Loss Carryforwards [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLossCarryforwards', window );">Net operating loss carryforwards</a></td>
<td class="nump">290.2<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxAuthorityAxis=us-gaap_StateAndLocalJurisdictionMember', window );">State [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLossCarryforwardsLineItems', window );"><strong>Operating Loss Carryforwards [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLossCarryforwards', window );">Net operating loss carryforwards</a></td>
<td class="nump">$ 526.9<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLossCarryforwards">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of operating loss carryforward, before tax effects, available to reduce future taxable income under enacted tax laws.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLossCarryforwards</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLossCarryforwardsLineItems">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLossCarryforwardsLineItems</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TaxCreditCarryforwardAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of the tax credit carryforward, before tax effects, available to reduce future taxable income under enacted tax laws.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TaxCreditCarryforwardAmount</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TaxCreditCarryforwardLineItems</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_InternalRevenueServiceIRSMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_CaliforniaFranchiseTaxBoardMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxAuthorityAxis=us-gaap_DomesticCountryMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxAuthorityAxis=us-gaap_StateAndLocalJurisdictionMember</td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367927051568">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Gross Unrecognized Tax Benefits (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ReconciliationOfUnrecognizedTaxBenefitsExcludingAmountsPertainingToExaminedTaxReturnsRollForward', window );"><strong>Gross Unrecognized Tax Benefits [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefits', window );">Beginning balance of unrecognized tax benefits</a></td>
<td class="nump">$ 43,298<span></span>
</td>
<td class="nump">$ 56,567<span></span>
</td>
<td class="nump">$ 55,085<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations', window );">Decrease for lapse of statute of limitations</a></td>
<td class="num">(7,579)<span></span>
</td>
<td class="num">(14,993)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions', window );">Decrease for prior period tax positions</a></td>
<td class="num">(110)<span></span>
</td>
<td class="num">(737)<span></span>
</td>
<td class="num">(267)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions', window );">Increase for prior period tax positions</a></td>
<td class="nump">1,902<span></span>
</td>
<td class="nump">429<span></span>
</td>
<td class="nump">259<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions', window );">Increase for current period tax positions</a></td>
<td class="nump">3,650<span></span>
</td>
<td class="nump">2,032<span></span>
</td>
<td class="nump">1,490<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefits', window );">Ending balance of unrecognized tax benefits</a></td>
<td class="nump">41,161<span></span>
</td>
<td class="nump">43,298<span></span>
</td>
<td class="nump">56,567<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate', window );">Unrecognized tax benefits that could impact effective tax rate, if recognized</a></td>
<td class="nump">300<span></span>
</td>
<td class="nump">300<span></span>
</td>
<td class="nump">6,200<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense', window );">Interest and penalties on gross unrecognized tax benefits</a></td>
<td class="nump">$ 100<span></span>
</td>
<td class="nump">$ 100<span></span>
</td>
<td class="nump">$ 800<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ReconciliationOfUnrecognizedTaxBenefitsExcludingAmountsPertainingToExaminedTaxReturnsRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ReconciliationOfUnrecognizedTaxBenefitsExcludingAmountsPertainingToExaminedTaxReturnsRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefits">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of unrecognized tax benefits.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 217<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-217<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-15A<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10B<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482525/740-10-45-10B<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefits</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of decrease in unrecognized tax benefits resulting from tax positions taken in prior period tax returns.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 217<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-217<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-15A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of expense for interest on an underpayment of income taxes and penalties related to a tax position claimed or expected to be claimed in the tax return.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 217<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-217<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase in unrecognized tax benefits resulting from tax positions that have been or will be taken in current period tax return.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 217<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-217<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-15A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase in unrecognized tax benefits resulting from tax positions taken in prior period tax returns.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 217<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-217<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-15A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of decrease in unrecognized tax benefits resulting from lapses of applicable statutes of limitations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(4)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-15A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The total amount of unrecognized tax benefits that, if recognized, would affect the effective tax rate.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 217<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-217<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-15A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367930195104">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Employment Benefits (Details) - USD ($)<br></strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract', window );"><strong>Employee Benefits [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DefinedContributionPlanCostRecognized', window );">Matching contributions</a></td>
<td class="nump">$ 8,600,000<span></span>
</td>
<td class="nump">$ 7,100,000<span></span>
</td>
<td class="nump">$ 5,600,000<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_RangeAxis=srt_MinimumMember', window );">Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract', window );"><strong>Employee Benefits [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount', window );">Employee contribution limit per calendar year</a></td>
<td class="nump">23,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_RangeAxis=srt_MaximumMember', window );">Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract', window );"><strong>Employee Benefits [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount', window );">Employee contribution limit per calendar year</a></td>
<td class="nump">$ 30,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost for defined contribution plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 715<br> -SubTopic 70<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480794/715-70-50-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DefinedContributionPlanCostRecognized</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Maximum amount the employee may contribute to a defined contribution plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount</td>
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<td>debit</td>
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<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>xbrli:stringItemType</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367926218272">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Segment Information (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($) </div>
<div>Segment</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SegmentReportingInformationProfitLossAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NumberOfOperatingSegments', window );">Number of operating segments | Segment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 705,138<span></span>
</td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostOfGoodsAndServicesSold', window );">Cost of sales</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11,215<span></span>
</td>
<td class="nump">9,133<span></span>
</td>
<td class="nump">14,116<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SellingGeneralAndAdministrativeExpense', window );">Selling, general and administrative</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">267,474<span></span>
</td>
<td class="nump">232,619<span></span>
</td>
<td class="nump">150,295<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (104,349)<span></span>
</td>
<td class="num">$ (9,263)<span></span>
</td>
<td class="num">$ (453,897)<span></span>
</td>
<td class="num">(366,286)<span></span>
</td>
<td class="num">(269,722)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SegmentReportingOtherItemCompositionDescription', window );">Segment Reporting, Other Segment Item, Composition, Description</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Other segment items include stock-based compensation expense, investment income, interest expense, gain or loss on investments, other income or expense and income tax expense or benefit.<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementBusinessSegmentsAxis=ions_IonisOperationsMember', window );">Ionis Operations [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SegmentReportingInformationProfitLossAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 705,138<span></span>
</td>
<td class="nump">787,647<span></span>
</td>
<td class="nump">587,367<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostOfGoodsAndServicesSold', window );">Cost of sales</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,415<span></span>
</td>
<td class="nump">8,686<span></span>
</td>
<td class="nump">13,447<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DrugDiscoveryExpenses', window );">Drug discovery</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">114,350<span></span>
</td>
<td class="nump">125,649<span></span>
</td>
<td class="nump">181,302<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DrugDevelopmentExpenses', window );">Drug development</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">527,259<span></span>
</td>
<td class="nump">530,332<span></span>
</td>
<td class="nump">426,225<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MedicalAffairsExpenses', window );">Medical affairs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">27,229<span></span>
</td>
<td class="nump">19,454<span></span>
</td>
<td class="nump">15,948<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ManufacturingAndDevelopmentChemistryExpenses', window );">Manufacturing and development chemistry</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">57,729<span></span>
</td>
<td class="nump">65,293<span></span>
</td>
<td class="nump">76,162<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ResearchAndDevelopmentSupportExpenses', window );">R&amp;D support</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">82,559<span></span>
</td>
<td class="nump">81,019<span></span>
</td>
<td class="nump">59,840<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SellingGeneralAndAdministrativeExpense', window );">Selling, general and administrative</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">230,478<span></span>
</td>
<td class="nump">205,135<span></span>
</td>
<td class="nump">124,370<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SegmentReportingOtherItemAmount', window );">Other segment items</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">109,016<span></span>
</td>
<td class="nump">118,365<span></span>
</td>
<td class="num">(40,205)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (453,897)<span></span>
</td>
<td class="num">$ (366,286)<span></span>
</td>
<td class="num">$ (269,722)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DrugDevelopmentExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Expenses related to drug development, including expenses for marketed medicines and those in Phase 3 development.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DrugDevelopmentExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DrugDiscoveryExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Expenses related to drug discovery research and advancing the Company's core technology.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DrugDiscoveryExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ManufacturingAndDevelopmentChemistryExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Expenses related to manufacturing and development chemistry for providing drug supplies to drug development and our collaboration partners, including personnel costs, specialized chemicals for oligonucleotide manufacturing, validation batches to support regulatory approvals, laboratory supplies and outside services.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ManufacturingAndDevelopmentChemistryExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MedicalAffairsExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Expenses related to medical affairs for funding and coordinating investigator-sponsored trials, communicating scientific and clinical information to healthcare providers, medical professionals and patients, and managing publications.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MedicalAffairsExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ResearchAndDevelopmentSupportExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Expenses related to research and development support such as rent, repair and maintenance for buildings and equipment, utilities, depreciation of laboratory equipment and facilities, amortization of intellectual property, information technology costs, procurement costs and waste disposal costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ResearchAndDevelopmentSupportExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostOfGoodsAndServicesSold">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate costs related to goods produced and sold and services rendered by an entity during the reporting period. This excludes costs incurred during the reporting period related to financial services rendered and other revenue generating activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(2)(d))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(2)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostOfGoodsAndServicesSold</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NumberOfOperatingSegments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of operating segments. An operating segment is a component of an enterprise: (a) that engages in business activities from which it may earn revenues and incur expenses (including revenues and expenses relating to transactions with other components of the same enterprise), (b) whose operating results are regularly reviewed by the enterprise's chief operating decision maker to make decisions about resources to be allocated to the segment and assess its performance, and (c) for which discrete financial information is available. An operating segment may engage in business activities for which it has yet to earn revenues, for example, start-up operations may be operating segments before earning revenues.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 49<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-49<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-18<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NumberOfOperatingSegments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of other expense (income) and loss (gain) calculated as difference between segment revenue and separately disclosed expense category to arrive at segment profit (loss).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 48<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-48<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 26C<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-26C<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 26B<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-26B<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Description of composition of other segment item not separately disclosed.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 48<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-48<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 26C<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-26C<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 26B<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-26B<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate total costs related to selling a firm's product and services, as well as all other general and administrative expenses. Direct selling expenses (for example, credit, warranty, and advertising) are expenses that can be directly linked to the sale of specific products. Indirect selling expenses are expenses that cannot be directly linked to the sale of specific products, for example telephone expenses, Internet, and postal charges. General and administrative expenses include salaries of non-sales personnel, rent, utilities, communication, etc.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br></p></div>
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<span style="display: none;">v3.25.0.1</span><table class="report" border="0" cellspacing="2" id="idm45367928101312">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fourth Quarter Financial Data (Unaudited) (Details) - USD ($)<br> $ / shares in Units, $ in Thousands</strong></div></th>
<th class="th" colspan="4">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th" colspan="2"><div>Dec. 31, 2024</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SelectedQuarterlyFinancialInformationAbstract', window );"><strong>Fourth Quarter Financial Data (Unaudited) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Revenues', window );">Revenue</a></td>
<td class="nump">$ 226,577<span></span>
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<td class="fn" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 324,505<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Operating expenses</a></td>
<td class="nump">337,398<span></span>
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<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">330,627<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 1,180,219<span></span>
</td>
<td class="nump">$ 1,141,377<span></span>
</td>
<td class="nump">$ 997,558<span></span>
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<tr class="rou">
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<td class="num">(110,821)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(6,122)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(475,081)<span></span>
</td>
<td class="num">(353,730)<span></span>
</td>
<td class="num">(410,191)<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (104,349)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (9,263)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (453,897)<span></span>
</td>
<td class="num">$ (366,286)<span></span>
</td>
<td class="num">$ (269,722)<span></span>
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<tr class="ro">
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<td class="num">$ (0.66)<span></span>
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<td class="fn" style="border-bottom: 0px;"><sup>[3],[4]</sup></td>
<td class="num">$ (0.06)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3],[4]</sup></td>
<td class="num">$ (3.04)<span></span>
</td>
<td class="num">$ (2.56)<span></span>
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<td class="num">$ (1.9)<span></span>
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<td class="num">$ (0.66)<span></span>
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<td class="fn" style="border-bottom: 0px;"><sup>[3],[5]</sup></td>
<td class="num">$ (0.06)<span></span>
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<td class="fn" style="border-bottom: 0px;"><sup>[3],[5]</sup></td>
<td class="num">$ (3.04)<span></span>
</td>
<td class="num">$ (2.56)<span></span>
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<td class="num">$ (1.9)<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember', window );">WAINUA [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SelectedQuarterlyFinancialInformationAbstract', window );"><strong>Fourth Quarter Financial Data (Unaudited) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Revenues', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 50,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember', window );">Cardiovascular, Renal and Metabolic Diseases [Member] | ION826 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SelectedQuarterlyFinancialInformationAbstract', window );"><strong>Fourth Quarter Financial Data (Unaudited) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Revenues', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 36,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="8"></td></tr>
<tr><td colspan="8"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue was lower in the three months ended December 31, 2024 compared to the same period in 2023 primarily due to significant partner payments earned in the fourth quarter of 2023, including the $</span>50<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment we earned from AstraZeneca when the FDA
              approved WAINUA for ATTRv-PN in the U.S., $</span>36<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
              million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis. </span>In addition, WAINUA
            joint development revenue decreased in the three months ended December 31, 2024 compared to the same period in 2023 as development activities relating to ATTRv-PN wound down with the launch of WAINUA.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Operating expenses were relatively consistent in the three months
            ended December 31, 2024 compared to the same period in 2023.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </span>compute net loss per share independently for each quarter during <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</span></td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[4]</td>
<td style="vertical-align: top;" valign="top">As discussed in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies, </span>we compute basic net loss per share by dividing the total net loss by our weighted-average number of common shares outstanding
            during the period.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[5]</td>
<td style="vertical-align: top;" valign="top">We incurred a net loss for the fourth quarter of 2024 and 2023. As a
            result, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive.</td>
</tr>
</table></td></tr>
</table>
<div style="display: none;">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total costs of sales and operating expenses for the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-6<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 52<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482635/260-10-55-52<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 805<br> -SubTopic 60<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (g)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147476176/805-60-65-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 323<br> -Name 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period available to each share of common stock or common unit outstanding during the reporting period and to each share or unit that would have been outstanding assuming the issuance of common shares or units for all dilutive potential common shares or units outstanding during the reporting period.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The net result for the period of deducting operating expenses from operating revenues.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingIncomeLoss</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Revenues">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of revenue recognized from goods sold, services rendered, insurance premiums, or other activities that constitute an earning process. Includes, but is not limited to, investment and interest income before deduction of interest expense when recognized as a component of revenue, and sales and trading gain (loss).</p></div>
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Risk management and strategy&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have implemented and maintain various information security processes designed to detect, respond to, recover, and protect our
    technology ecosystem from cybersecurity threats. These processes are designed to identify, assess, and manage material risks that may result from cybersecurity threats and apply to our critical technologies inclusive of networks, third party hosted
    services, communications systems, hardware, software, and critical data, including intellectual property and confidential information that is proprietary, strategic, or competitive in nature.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our Information Technology department, led by our Senior Vice President, Information Technology, helps to detect, respond to, and manage
    cybersecurity threats and risks by monitoring and evaluating our threat environment using various manual and automated tools in certain environments and systems and other methods including, for example:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;analyzing reports of certain threats and actors;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;conducting scans of the threat environment;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;evaluating our and our industry&#x2019;s risk profile;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;evaluating certain threats reported to us;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;conducting internal and external audits;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;conducting threat assessments for certain internal and external threats; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;conducting vulnerability assessments designed to identify vulnerabilities.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Depending on the environment, system and data, we have implemented and maintain various technical, physical, and organizational measures,
    processes, standards, and policies designed to manage and mitigate material risks from cybersecurity threats to our critical technologies and data, including, for example:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;incident response plan;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;disaster recovery/business continuity plans;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;risk assessments;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;encryption of certain data;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;network security and access controls for certain systems;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;physical security;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;asset management, tracking and disposal;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;systems monitoring; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;employee training.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our assessment and management of material risks from cybersecurity threats are integrated into the Company&#x2019;s overall risk management processes. For example, cybersecurity risk is assessed as a component of our enterprise risk
    management program. In addition, we have developed a process whereby our senior management evaluates material risks from cybersecurity threats against our overall business objectives and reports certain cybersecurity incidents to the Audit Committee of
    the Board of Directors, which evaluates our overall enterprise risk. &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use third-party providers to perform various functions throughout our business, such as application providers and hosting companies. We use third-party providers to assist us from time to time in an effort to identify, assess, and manage material risks from cybersecurity threats, including, for example, legal counsel, cybersecurity consultants, cybersecurity software providers, penetration testing firms, and forensic investigators.&#160;The Company maintains a risk-based approach and process designed to identify and oversee cybersecurity risks presented by third parties, including vendors, service providers and other external users of the Company&#x2019;s systems, as well as the systems of third parties that could materially impact our business if there is a cybersecurity incident affecting those third-party systems.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For an additional description of the risks from cybersecurity
    threats that may materially affect us and how they may do so, see our risk factors under Item 1A, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Risk Factors&lt;/span&gt;, in this Annual Report on Form 10-K, including the risk factor titled &#x201c;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;We are
      dependent on data as well as information technology systems and infrastructure, which exposes us to data protection risks&lt;/span&gt;.&#x201d;&lt;/div&gt;
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&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our assessment and management of material risks from cybersecurity threats are integrated into the Company&#x2019;s overall risk management processes. For example, cybersecurity risk is assessed as a component of our enterprise risk
    management program. In addition, we have developed a process whereby our senior management evaluates material risks from cybersecurity threats against our overall business objectives and reports certain cybersecurity incidents to the Audit Committee of
    the Board of Directors, which evaluates our overall enterprise risk. &lt;/div&gt;
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&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For an additional description of the risks from cybersecurity
    threats that may materially affect us and how they may do so, see our risk factors under Item 1A, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Risk Factors&lt;/span&gt;, in this Annual Report on Form 10-K, including the risk factor titled &#x201c;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;We are
      dependent on data as well as information technology systems and infrastructure, which exposes us to data protection risks&lt;/span&gt;.&#x201d;&lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our Board of Directors addresses our cybersecurity risk management as part of its general oversight function. &lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;The Audit Committee of the Board of Directors is responsible for overseeing our cybersecurity risk management processes, including oversight and mitigation of risks from cybersecurity threats.&lt;/span&gt; The Audit Committee also oversees our internal audit department and management&#x2019;s internal controls over financial reporting, including with respect to cybersecurity.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cybersecurity risk assessment and management processes are implemented and maintained by our Senior Vice President, Information Technology, &lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;who holds an undergraduate
    degree in Computer Engineering and has served in information technology and security roles dedicated to the pharmaceutical and biotechnology sector for approximately 18 years, including serving as the Chief Information Officer of two public
    biopharmaceutical companies.&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our Senior Vice President, Information Technology is
    responsible for hiring appropriate personnel, helping to integrate cybersecurity risk considerations into our overall risk management strategy, communicating key priorities to relevant personnel, helping prepare for cybersecurity incidents, approving
    cybersecurity processes, and reviewing security assessments and other security-related reports.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cybersecurity incident response plan is designed to
    escalate certain cybersecurity incidents, depending on the circumstances, to our senior management team and Audit Committee of the Board of Directors. The Audit Committee of the Board of Directors receives reports from our Senior Vice President, Information Technology concerning our significant cybersecurity threats and risks (including certain cybersecurity threats) and the processes we
    have implemented that are designed to address them. &lt;/div&gt;
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&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cybersecurity risk assessment and management processes are implemented and maintained by our Senior Vice President, Information Technology, &lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;who holds an undergraduate
    degree in Computer Engineering and has served in information technology and security roles dedicated to the pharmaceutical and biotechnology sector for approximately 18 years, including serving as the Chief Information Officer of two public
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&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our Senior Vice President, Information Technology is
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&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our Senior Vice President, Information Technology is
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&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cybersecurity incident response plan is designed to
    escalate certain cybersecurity incidents, depending on the circumstances, to our senior management team and Audit Committee of the Board of Directors. The Audit Committee of the Board of Directors receives reports from our Senior Vice President, Information Technology concerning our significant cybersecurity threats and risks (including certain cybersecurity threats) and the processes we
    have implemented that are designed to address them. &lt;/div&gt;
</cyd:CybersecurityRiskProcessForInformingBoardCommitteeOrSubcommitteeResponsibleForOversightTextBlock>
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the quarter ended December 31, 2024, our
    directors and officers (as defined in Rule 16a-1(f) under the Exchange Act), or Section 16 officers and directors, adopted or terminated contracts, instructions or written plans for the purchase or sale of our securities as noted in the table below.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;*&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Contract, instruction or written plan intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) under the Exchange Act.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;**&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x201c;Non-Rule 10b5-1 trading arrangement&#x201d; as defined in item 408(c) of Regulation S-K under the Exchange Act.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

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  &lt;tr&gt;

    &lt;td rowspan="2" style="width: 22%; vertical-align: bottom;"&gt; &lt;/td&gt;

    &lt;td rowspan="2" style="width: 1%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

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    &lt;td rowspan="2" style="width: 0.66%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td rowspan="2" style="width: 15.54%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Date&lt;/div&gt;
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    &lt;td rowspan="2" style="width: 1.21%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="3" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;
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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt; to be Sold&lt;/div&gt;
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    &lt;td rowspan="2" style="width: 0.93%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Expiration Date&lt;/div&gt;
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  &lt;/tr&gt;

  &lt;tr&gt;

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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Rule 10b5-1*&lt;/div&gt;
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    &lt;td style="width: 1.46%; vertical-align: bottom; border-top: #000000 2px solid;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 10%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Non-Rule 10b5-1**&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 22%; vertical-align: bottom; background-color: rgb(204, 238, 255);"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Joseph Wender, Board Member&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 1%; vertical-align: top; background-color: rgb(204, 238, 255);"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 10%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_4da096b126c946ab97fa70bd9a39f088"&gt;Adoption&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 0.66%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 15.54%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;December 26, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 1.21%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 10%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;X&lt;/div&gt;
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    &lt;td style="width: 1.46%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 1.06%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 9.83%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,079&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 0.93%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 16%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;February 28, 2026&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1. Organization and Significant Accounting Policies&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basis of Presentation&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;).&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Organization and Business Activity&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We incorporated in California on January 10, 1989. In conjunction with our IPO, we reorganized as a Delaware corporation in April 1991. We
    were organized principally to develop human therapeutic medicines using antisense technology. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We operate as a &lt;span style="-sec-ix-hidden:Fact_0a919095f48f42f79abafacb21f6d831"&gt;single&lt;/span&gt; segment, Ionis
    operations, because our chief operating decision maker, or CODM, reviews operating results on an aggregate basis and manages our operations as a single operating segment. Refer to Note 12, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Segment Information&lt;/span&gt;, for further details on our segment information.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Use of Estimates&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the United States, or
    U.S., that require us to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Revenue Recognition&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting
    receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include
    the amounts within deferred revenue in our consolidated balance sheets.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities
    performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC,
    Topic 808, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements&lt;/span&gt;, or ASC 808. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;ASC &lt;/span&gt;808&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration
      arrangements within the scope of ASC &lt;/span&gt;808&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; that contain multiple elements, we &lt;/span&gt;first&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;
      determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC &lt;/span&gt;606&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Revenue from Contracts with Customers&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. When we determine elements of a collaboration do not
      reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with
    multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our WAINUA collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue; while
    we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as selling, general and administrative, or SG&amp;amp;A, expense and research and development, or R&amp;amp;D, expense,
    respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Steps to Recognize Revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of
    revenue we should recognize and when we should recognize it. The five-step process is as follows:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;1.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Identify the contract&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accounting rules require us to first determine if we have a contract with our partner or customer.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;2.&lt;/span&gt;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Identify the performance obligations&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the
    contract.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;3.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Determine the transaction price&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration
      agreement, including any variable consideration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;4.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Allocate the transaction price&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Next, we allocate the transaction price to each of our
        performance obligations. When we have to allocate the transaction price to more than &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; performance obligation, we make estimates of the relative stand-alone
        selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do
        not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;5.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Recognize revenue&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize revenue in &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; ways, over time or at a point in time. We recognize revenue over time when we are executing on our
        performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a
        specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue, which
      in certain cases may require us to estimate our royalty revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Amendments to Agreements&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the
    accounting for the amendment:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the goods and/or services are sold at a stand-alone selling price.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at
      a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are
      distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment
      to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a
      cumulative-effect adjustment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Multiple agreements&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to
    determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the goods and/or services promised under the agreements are a single performance obligation.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting
    guidance requires us to account for them as a combined arrangement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Refer to Note 4, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative
      Arrangements and Licensing Agreements&lt;/span&gt;, for further discussion of our 2018 neurology collaboration with Biogen that included multiple agreements which we negotiated concurrently and in contemplation of one another.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contracts Receivable&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our contracts receivable balance represents the amounts we
      have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts
      receivable to be unconditional. We typically receive payment within &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;quarter of billing our partner or customer&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2024,
    approximately 95.6 percent of our contracts receivables were from three significant customers. As of December 31, 2023, approximately 87.8 percent of our contracts receivables were from one
    significant customer.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unbilled Royalties&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our unbilled royalties represent our right to receive consideration from our partners in advance of when we are eligible to bill them for
    royalties. We include these unbilled amounts in other current assets in our consolidated balance sheets.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Deferred Revenue&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are often entitled to bill our customers and receive
      payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue in our consolidated balance sheets.&lt;/span&gt; During the years ended December 31, 2024 and 2023, we recognized $166.1 million and $78.2 million of revenue from
    amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Sales&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs
    and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Research, Development and Patent Expenses&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and
    manufacturing costs, patents and other expenses that are directly related to our R&amp;amp;D operations. We expense R&amp;amp;D costs as we incur them. When we make payments for R&amp;amp;D services prior to the services being rendered, we record those amounts as
    prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in R&amp;amp;D expenses are costs associated with our partner agreements. In 2024, 2023 and 2022, patent expenses were $5.3 million, $4.3 million and $4.7 million, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income Taxes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities
    for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development
    credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and
    measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight
    of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit
    as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes.
    Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these
    reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the
    provision for income taxes in the period in which we make such determination.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In
    assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We
    base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from
    our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be
    realized. &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic and Diluted Net Loss per Share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Basic net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We compute basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the
    period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Diluted net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2024,
    2023 and 2022, we incurred a net
    loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss
    per share:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes, or &lt;/span&gt;0%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note hedges related to the &lt;/span&gt;0%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes, or &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note hedges related to the &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dilutive stock options;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested restricted stock units, or RSUs;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested performance restricted stock units, or PRSUs; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Employee Stock Purchase Plan, or ESPP.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2024 and 2023, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, would also
    have had an anti-dilutive effect on net loss per share.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;As of December 31, 2024, 2023 and 2022, we had outstanding warrants related to our 0% Notes and 0.125% Notes. We will include the shares issuable
    under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.&lt;/span&gt; During 2024, 2023 and 2022, the market price
    of our common stock did not exceed the strike price of the warrants.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock-Based Compensation Expense&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock
    purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service
    period in our consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated
    multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award
    were in substance multiple awards, which results in the expense being front-loaded over the vesting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Stock Options and Stock Purchase Rights:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant
    date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the
    awards, and actual and projected employee stock option exercise behaviors. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted
    based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options
    granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this
    change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the years ended December 31, 2024, 2023 and 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we
    gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;RSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest
    annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. The annual RSUs we granted to our board of directors after June 2020 fully vest after one year. The RSUs we granted to board members at their initial appointment to the board of directors vest annually over a three-year period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;PRSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added
    PRSU awards to the compensation for our other Section 16 officers. Under the terms of the PRSUs we granted in 2020 through 2022, &lt;span style="-sec-ix-hidden:Fact_65d15117ab79462e81dfb8bbb86a0107"&gt;&lt;span style="-sec-ix-hidden:Fact_e9934b85c6af480197be8d0d8b5ea434"&gt;&lt;span style="-sec-ix-hidden:Fact_5599af32346c4fce91fa6d27caf4b474"&gt;one third&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;
    of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period
    commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant
    and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third
    anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 150 percent of the target number
    depending on our relative TSR. These PRSU awards also included an alternative three-year payout mechanism, or the Alternative Calculation, under
    which we must calculate an alternative payout at the end of the final three-year measurement period assuming the only measurement period for all
    shares under the award was the three-year period. If the Alternative Calculation is greater than payouts under the sum of the three years, then such PRSU award will pay out to achieve the number of shares payable under the Alternative Calculation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under the terms of the PRSUs we granted in 2024 and 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period based on our relative TSR as
    compared to a peer group of companies and as measured at the end of the performance period. Under the terms of the grants, no number of PRSUs is
    guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 200 percent of the target number depending on our relative TSR.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determine the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which
    represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Refer to Note 8, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Stockholders&#x2019; Equity,&lt;/span&gt;
    for additional information regarding our stock-based compensation plans.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Concentration of Credit Risk&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term
    investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions,
    corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#x2019;s, Standard &amp;amp; Poor&#x2019;s, or S&amp;amp;P, or Fitch, respectively. We have established guidelines relative to
    diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value Measurements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and
    accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1,
    defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly
    traded biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale
    securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments
    from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value
    to the fair value based on observable market prices.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cash, Cash Equivalents and Investments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term
    investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#x201c;available-for-sale&#x201d; and carry them at fair market value based upon prices on the last day of the fiscal period for
    identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our consolidated statements of
    operations. We use the specific identification method to determine the cost of securities sold.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also have equity investments of less than 20 percent ownership in public and private biotechnology companies that we received as part
      of a technology license or partner agreement. At December 31, 2024, we held equity investments in three publicly traded companies and seven privately held companies.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our consolidated
    statements of operations. We account for our equity investments in publicly traded companies at their listed stock price. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting
    from observable price changes in orderly transactions for the identical or similar investment of the same issuer.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Inventories&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We reflect our inventory in our consolidated balance sheets at the lower of cost or net realizable value under the first-in, first-out
    method, or FIFO. Our inventory costs include material, labor and overhead costs. Our raw materials include active pharmaceutical ingredient, or API, for commercial medicines. We capitalize inventory costs related to drug products when we consider
    future commercialization to be probable and expect to realize future economic benefit. When evaluating whether to capitalize inventory costs, we consider various factors, including the likelihood of receiving required regulatory approvals,
    communications from regulatory agencies such as safety or efficacy concerns, underlying manufacturing processes and supply chain matters, shelf life of the inventory, market trends such as competition and pricing, potential legal matters and potential
    reimbursement strategies. We record inventory costs that do not meet our capitalization requirements as R&amp;amp;D expense in our consolidated statements of operations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated
    net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory and historical write-offs.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Capitalized Materials&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We capitalize the costs of certain materials that we purchase for use in manufacturing our medicines in our clinical development programs
    because until we use these materials, they have alternative future uses. We can use these materials in multiple products and, as a result, each material has future economic value independent of the development status of any single medicine. We include
    capitalized materials in other current assets in our consolidated balance sheets and expense these costs as R&amp;amp;D expenses when the materials are used. We review our capitalized materials periodically for continued alternative future use and reduce
    the carrying value of items in the period in which an impairment is identified.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2024, we reclassified capitalized costs related to materials used in our clinical development programs from inventories to other
    current assets in our consolidated balance sheets. As such, we reclassified the respective prior period amounts to conform with the current year presentation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Property, Plant and Equipment&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which we
    determine as the following (in years):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt; &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Useful Lives&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Computer software, laboratory, manufacturing and other equipment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3 to 10&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Building, building improvements and building systems&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15 to 40&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Leasehold improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 15&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Furniture and fixtures&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 10&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived
    assets, which include property, plant and equipment, for impairment whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Accrued Liabilities&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. We estimate our liability
    for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to third-party clinical management
    costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted
    fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these costs may differ
    materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Convertible Debt&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We account for each of our convertible debt instruments as a
      single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt
      issuance costs as contra-liabilities in our consolidated balance sheets at issuance and amortize them over the contractual term of the convertible debt instrument using the effective interest rate. &lt;/span&gt;The&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; balances of our convertible senior notes presented in our consolidated balance sheets represent the principal balance of each convertible debt instrument less debt issuance costs.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2024, we
    had two outstanding convertible senior notes, our 1.75%
    Notes, which mature in June 2028, and our 0% Notes, which mature in April 2026. Our 0.125% Notes matured in December 2024. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term Obligations and
      Commitments&lt;/span&gt;, for further details on our convertible senior notes.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with the issuance of our 0%
    Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of
    purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not
    meet the definition of a liability using the guidance contained in ASC Topic 480; therefore, we account for the note hedges and warrants using the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Derivatives







      and Hedging &#x2013; Contracts in Entity&#x2019;s Own Equity&lt;/span&gt; accounting guidance contained in ASC Topic 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified
    in shareholders&#x2019; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our consolidated balance sheets. We reassess our ability to continue to classify any
    outstanding note hedges and warrants in shareholders&#x2019; equity at each reporting period. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term Obligations and Commitments&lt;/span&gt;, for
    further details on the call spread transactions. &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Liability Related to Sale of Future Royalties&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. Under our agreement with Royalty Pharma, we record upfront payments and milestone payments we receive from the sale of future
    royalties as a liability, net of transaction costs. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term Obligations and Commitments&lt;/span&gt;, for further details on the agreement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We record royalty payments made to Royalty Pharma as a reduction of the liability or accrued interest and amortize the transaction costs
    over the estimated life of the royalty stream. We account for the associated interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the
    related product and recognizes the related revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense using our
    current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material
    change in our estimate, we will prospectively adjust the effective interest rate and the related interest expense.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use
    operating lease asset and associated short- and long-term operating lease liability in our consolidated balance sheets for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term
    and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we
    will pay over the lease term.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&#160;&lt;/span&gt;We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal
    options if we conclude we are reasonably certain to exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease
    term.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information
    available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease.
    Our leases do not include material variable or contingent lease payments. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Recent Accounting Standards&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2023, the Financial Accounting Standards Board, or FASB, issued Accounting Standard Update, or ASU, 2023-07, which provides
    updated guidance on segment reporting. The guidance requires public companies to disclose significant expenses that are regularly provided to the CODM, other segment items for each reportable segment and measures of segment profit or loss used by the
    CODM for allocating resources. In addition, the updated guidance requires public companies with a single reportable segment to provide all disclosures required under ASC 280, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Segment Reporting&lt;/span&gt;, and public companies to include in interim reports all disclosures related to a reportable segment&#x2019;s profit or loss and assets that are currently required in annual reports. This update is effective for
    annual periods beginning after December 15, 2023 and interim periods beginning after December 15, 2024. The guidance is applied on a retrospective basis for all periods presented in the financial statements, unless it is impracticable. We adopted the
    annual reporting requirements in our 2024 Annual Report on Form 10-K. We expect to adopt the interim reporting requirements in our Quarterly Report on Form 10-Q in the first quarter of 2025. Refer to Note 12, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Segment Information&lt;/span&gt;, for further details on our segment information.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2023, the FASB issued ASU 2023-09, which provides updated guidance on income tax disclosures. The new guidance requires
    companies to provide additional disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions and
    unrecognized deferred tax liabilities. This update is effective for annual periods beginning after December 15, 2024. Early adoption of this guidance is permitted. The guidance may be applied on a prospective or retrospective basis. We currently plan
    to adopt this guidance in our 2025 Annual Report on Form 10-K.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2024, the FASB issued ASU 2024-03, which requires public companies to disclose disaggregated expenses for certain expenses in
    the income statement. This update is effective for annual periods beginning after December 15, 2026 and interim periods within annual periods beginning after December 15, 2027. Early adoption of this guidance is permitted. The guidance may be applied
    on a prospective or retrospective basis. We are currently assessing the impact and timing of adopting this update.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2024, the FASB issued ASU 2024-04 to clarify the guidance for determining whether to account for early settlements of
    convertible debt as induced conversions or extinguishments. This update is effective for annual periods beginning after December 15, 2025 and interim periods within those annual periods. Early adoption of this guidance is permitted. The guidance may be
    applied on a prospective or retrospective basis. We are currently assessing the impact and timing of adopting this update.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not expect any other recently issued accounting standards to have a material impact to our financial statements or disclosures.&lt;/div&gt;
</us-gaap:OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTextBlock>
    <us-gaap:ConsolidationPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_f9a3c5dc257b427aabe07dd4809eeb67">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basis of Presentation&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;).&lt;/div&gt;
</us-gaap:ConsolidationPolicyTextBlock>
    <us-gaap:SegmentReportingPolicyPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_1f633c4a698f418f8aaba786d26a86aa">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We operate as a &lt;span style="-sec-ix-hidden:Fact_0a919095f48f42f79abafacb21f6d831"&gt;single&lt;/span&gt; segment, Ionis
    operations, because our chief operating decision maker, or CODM, reviews operating results on an aggregate basis and manages our operations as a single operating segment. Refer to Note 12, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Segment Information&lt;/span&gt;, for further details on our segment information.&lt;/div&gt;
</us-gaap:SegmentReportingPolicyPolicyTextBlock>
    <us-gaap:UseOfEstimates
      contextRef="c20240101to20241231"
      id="Text_1fd01a87e7da42ebb9f72e4dc40a543b">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Use of Estimates&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the United States, or
    U.S., that require us to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates.&lt;/div&gt;
</us-gaap:UseOfEstimates>
    <us-gaap:RevenueFromContractWithCustomerPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_774eb668f2cd4ae1bbca4e764a581e35">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Revenue Recognition&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting
    receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include
    the amounts within deferred revenue in our consolidated balance sheets.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities
    performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC,
    Topic 808, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements&lt;/span&gt;, or ASC 808. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;ASC &lt;/span&gt;808&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration
      arrangements within the scope of ASC &lt;/span&gt;808&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; that contain multiple elements, we &lt;/span&gt;first&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;
      determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC &lt;/span&gt;606&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Revenue from Contracts with Customers&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. When we determine elements of a collaboration do not
      reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with
    multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our WAINUA collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue; while
    we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as selling, general and administrative, or SG&amp;amp;A, expense and research and development, or R&amp;amp;D, expense,
    respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Steps to Recognize Revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of
    revenue we should recognize and when we should recognize it. The five-step process is as follows:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;1.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Identify the contract&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accounting rules require us to first determine if we have a contract with our partner or customer.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;2.&lt;/span&gt;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Identify the performance obligations&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the
    contract.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;3.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Determine the transaction price&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration
      agreement, including any variable consideration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;4.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Allocate the transaction price&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Next, we allocate the transaction price to each of our
        performance obligations. When we have to allocate the transaction price to more than &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; performance obligation, we make estimates of the relative stand-alone
        selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do
        not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;5.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Recognize revenue&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize revenue in &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; ways, over time or at a point in time. We recognize revenue over time when we are executing on our
        performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a
        specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue, which
      in certain cases may require us to estimate our royalty revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Amendments to Agreements&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the
    accounting for the amendment:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the goods and/or services are sold at a stand-alone selling price.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at
      a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are
      distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment
      to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a
      cumulative-effect adjustment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Multiple agreements&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to
    determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the goods and/or services promised under the agreements are a single performance obligation.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting
    guidance requires us to account for them as a combined arrangement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Refer to Note 4, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative
      Arrangements and Licensing Agreements&lt;/span&gt;, for further discussion of our 2018 neurology collaboration with Biogen that included multiple agreements which we negotiated concurrently and in contemplation of one another.&lt;/div&gt;
</us-gaap:RevenueFromContractWithCustomerPolicyTextBlock>
    <us-gaap:ReceivablesPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_5725e312987247ee863902943c0938c8">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contracts Receivable&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our contracts receivable balance represents the amounts we
      have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts
      receivable to be unconditional. We typically receive payment within &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;quarter of billing our partner or customer&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2024,
    approximately 95.6 percent of our contracts receivables were from three significant customers. As of December 31, 2023, approximately 87.8 percent of our contracts receivables were from one
    significant customer.&lt;/div&gt;
</us-gaap:ReceivablesPolicyTextBlock>
    <ions:NumberOfQuartersAfterBillingWhenPaymentIsReceived
      contextRef="c20240101to20241231"
      decimals="INF"
      id="Fact_13d4b765faea4f21b13d4310d6749429"
      unitRef="U006">1</ions:NumberOfQuartersAfterBillingWhenPaymentIsReceived>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20240101to20241231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_ThreeSignificantCustomersMember"
      decimals="3"
      id="Fact_10e7a43398a0499b9e7ce86d84750009"
      unitRef="U003">0.956</us-gaap:ConcentrationRiskPercentage1>
    <ions:NumberOfSignificantCustomers
      contextRef="c20240101to20241231"
      decimals="INF"
      id="Fact_fa43dcb0b8ee41488642917fbbe8ac66"
      unitRef="U007">3</ions:NumberOfSignificantCustomers>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_OneSignificantCustomerMember"
      decimals="3"
      id="Fact_bb586f81c8674dd6b924c9686075aa5b"
      unitRef="U003">0.878</us-gaap:ConcentrationRiskPercentage1>
    <ions:NumberOfSignificantCustomers
      contextRef="c20230101to20231231"
      decimals="INF"
      id="Fact_3f1c8550953d4fb1bbaac07917b18557"
      unitRef="U007">1</ions:NumberOfSignificantCustomers>
    <us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy
      contextRef="c20240101to20241231"
      id="Text_11c759b68b4b4c4b94628fcf39b9e913">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unbilled Royalties&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our unbilled royalties represent our right to receive consideration from our partners in advance of when we are eligible to bill them for
    royalties. We include these unbilled amounts in other current assets in our consolidated balance sheets.&lt;/div&gt;
</us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy>
    <us-gaap:RevenueRecognitionPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_4fad649cf4524327bf2658a3254aca30">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Deferred Revenue&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are often entitled to bill our customers and receive
      payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue in our consolidated balance sheets.&lt;/span&gt; During the years ended December 31, 2024 and 2023, we recognized $166.1 million and $78.2 million of revenue from
    amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.&lt;/div&gt;
</us-gaap:RevenueRecognitionPolicyTextBlock>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20240101to20241231"
      decimals="-5"
      id="Fact_7a9ec3bea8ad464ca6e12c6aa16435cd"
      unitRef="U001">166100000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20230101to20231231"
      decimals="-5"
      id="Fact_ced6b030f6d146bb91eabbce81e6f413"
      unitRef="U001">78200000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:CostOfSalesPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_7bb4849d286842ec8c69f3be8efe749c">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Sales&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs
    and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.&lt;/div&gt;
</us-gaap:CostOfSalesPolicyTextBlock>
    <us-gaap:ResearchAndDevelopmentExpensePolicy
      contextRef="c20240101to20241231"
      id="Text_3a1d8d5acce046e6b43dae80c783423c">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Research, Development and Patent Expenses&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and
    manufacturing costs, patents and other expenses that are directly related to our R&amp;amp;D operations. We expense R&amp;amp;D costs as we incur them. When we make payments for R&amp;amp;D services prior to the services being rendered, we record those amounts as
    prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in R&amp;amp;D expenses are costs associated with our partner agreements. In 2024, 2023 and 2022, patent expenses were $5.3 million, $4.3 million and $4.7 million, respectively.&lt;/div&gt;
</us-gaap:ResearchAndDevelopmentExpensePolicy>
    <ions:PatentExpenses
      contextRef="c20240101to20241231"
      decimals="-5"
      id="Fact_85866a721e84472989175bb6188f4c57"
      unitRef="U001">5300000</ions:PatentExpenses>
    <ions:PatentExpenses
      contextRef="c20230101to20231231"
      decimals="-5"
      id="Fact_a0ff596166e44c50ba79c8d446d1bb4e"
      unitRef="U001">4300000</ions:PatentExpenses>
    <ions:PatentExpenses
      contextRef="c20220101to20221231"
      decimals="-5"
      id="Fact_18be9a3bed5e4b5a815b9ba827f8eb2d"
      unitRef="U001">4700000</ions:PatentExpenses>
    <us-gaap:IncomeTaxPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_2b4437a3b045421c8ee586d057cb332a">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income Taxes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities
    for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development
    credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and
    measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight
    of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit
    as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes.
    Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these
    reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the
    provision for income taxes in the period in which we make such determination.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In
    assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We
    base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from
    our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be
    realized. &lt;/div&gt;
</us-gaap:IncomeTaxPolicyTextBlock>
    <us-gaap:EarningsPerSharePolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_47e97970a2d74b528c3d5e13d3b65bad">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic and Diluted Net Loss per Share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Basic net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We compute basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the
    period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Diluted net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2024,
    2023 and 2022, we incurred a net
    loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss
    per share:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes, or &lt;/span&gt;0%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note hedges related to the &lt;/span&gt;0%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes, or &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note hedges related to the &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dilutive stock options;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested restricted stock units, or RSUs;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested performance restricted stock units, or PRSUs; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Employee Stock Purchase Plan, or ESPP.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2024 and 2023, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, would also
    have had an anti-dilutive effect on net loss per share.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;
&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;As of December 31, 2024, 2023 and 2022, we had outstanding warrants related to our 0% Notes and 0.125% Notes. We will include the shares issuable
    under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.&lt;/span&gt;</us-gaap:EarningsPerSharePolicyTextBlock>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_73bfeee93f8546f5b370edd9f616a4d4"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_5c056baf11664eb8bb1412c9ff380ed0"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_f51d9adf928c4a84aaf14638a3b4ce14"
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock-Based Compensation Expense&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock
    purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service
    period in our consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated
    multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award
    were in substance multiple awards, which results in the expense being front-loaded over the vesting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Stock Options and Stock Purchase Rights:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant
    date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the
    awards, and actual and projected employee stock option exercise behaviors. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted
    based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options
    granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this
    change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the years ended December 31, 2024, 2023 and 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we
    gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;RSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest
    annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. The annual RSUs we granted to our board of directors after June 2020 fully vest after one year. The RSUs we granted to board members at their initial appointment to the board of directors vest annually over a three-year period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;PRSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added
    PRSU awards to the compensation for our other Section 16 officers. Under the terms of the PRSUs we granted in 2020 through 2022, &lt;span style="-sec-ix-hidden:Fact_65d15117ab79462e81dfb8bbb86a0107"&gt;&lt;span style="-sec-ix-hidden:Fact_e9934b85c6af480197be8d0d8b5ea434"&gt;&lt;span style="-sec-ix-hidden:Fact_5599af32346c4fce91fa6d27caf4b474"&gt;one third&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;
    of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period
    commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant
    and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third
    anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 150 percent of the target number
    depending on our relative TSR. These PRSU awards also included an alternative three-year payout mechanism, or the Alternative Calculation, under
    which we must calculate an alternative payout at the end of the final three-year measurement period assuming the only measurement period for all
    shares under the award was the three-year period. If the Alternative Calculation is greater than payouts under the sum of the three years, then such PRSU award will pay out to achieve the number of shares payable under the Alternative Calculation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under the terms of the PRSUs we granted in 2024 and 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period based on our relative TSR as
    compared to a peer group of companies and as measured at the end of the performance period. Under the terms of the grants, no number of PRSUs is
    guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 200 percent of the target number depending on our relative TSR.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determine the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which
    represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Refer to Note 8, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Stockholders&#x2019; Equity,&lt;/span&gt;
    for additional information regarding our stock-based compensation plans.&lt;/div&gt;
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    <ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest
      contextRef="c20240101to20241231_AwardDateAxis_GrantedIn2024And2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MinimumMember"
      decimals="INF"
      id="Fact_cef441d443044be391448d0eecd8a2b3"
      unitRef="U003">0</ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest>
    <ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest
      contextRef="c20240101to20241231_AwardDateAxis_GrantedIn2024And2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MaximumMember"
      decimals="2"
      id="Fact_c5042a913c244bf085af7da30aab1dff"
      unitRef="U003">2</ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest>
    <us-gaap:ConcentrationRiskCreditRisk
      contextRef="c20240101to20241231"
      id="Text_2657526565084c29a44990225a255af0">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Concentration of Credit Risk&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term
    investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions,
    corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#x2019;s, Standard &amp;amp; Poor&#x2019;s, or S&amp;amp;P, or Fitch, respectively. We have established guidelines relative to
    diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.&lt;/div&gt;
</us-gaap:ConcentrationRiskCreditRisk>
    <us-gaap:FairValueOfFinancialInstrumentsPolicy
      contextRef="c20240101to20241231"
      id="Text_1c1a3fa5b06c4f8eb0d08a8a2d8e1c26">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value Measurements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and
    accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1,
    defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly
    traded biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale
    securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments
    from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value
    to the fair value based on observable market prices.&lt;/div&gt;
</us-gaap:FairValueOfFinancialInstrumentsPolicy>
    <us-gaap:InvestmentPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_6331a27b92f04118a22313343e337534">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cash, Cash Equivalents and Investments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term
    investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#x201c;available-for-sale&#x201d; and carry them at fair market value based upon prices on the last day of the fiscal period for
    identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our consolidated statements of
    operations. We use the specific identification method to determine the cost of securities sold.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also have equity investments of less than 20 percent ownership in public and private biotechnology companies that we received as part
      of a technology license or partner agreement. At December 31, 2024, we held equity investments in three publicly traded companies and seven privately held companies.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our consolidated
    statements of operations. We account for our equity investments in publicly traded companies at their listed stock price. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting
    from observable price changes in orderly transactions for the identical or similar investment of the same issuer.&lt;/div&gt;
</us-gaap:InvestmentPolicyTextBlock>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20241231"
      decimals="INF"
      id="Fact_b448547c88c7434cbc329f97a4b3ea28"
      unitRef="U009">3</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20241231"
      decimals="INF"
      id="Fact_5091e6339b9e4e85943dd42b9d332383"
      unitRef="U009">7</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <us-gaap:InventoryPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_962b0a89596444369c91918399edde59">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Inventories&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We reflect our inventory in our consolidated balance sheets at the lower of cost or net realizable value under the first-in, first-out
    method, or FIFO. Our inventory costs include material, labor and overhead costs. Our raw materials include active pharmaceutical ingredient, or API, for commercial medicines. We capitalize inventory costs related to drug products when we consider
    future commercialization to be probable and expect to realize future economic benefit. When evaluating whether to capitalize inventory costs, we consider various factors, including the likelihood of receiving required regulatory approvals,
    communications from regulatory agencies such as safety or efficacy concerns, underlying manufacturing processes and supply chain matters, shelf life of the inventory, market trends such as competition and pricing, potential legal matters and potential
    reimbursement strategies. We record inventory costs that do not meet our capitalization requirements as R&amp;amp;D expense in our consolidated statements of operations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated
    net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory and historical write-offs.&lt;/div&gt;
</us-gaap:InventoryPolicyTextBlock>
    <ions:CapitalizedMaterialsPolicyPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_aeaa95f916fe470ebc4b35d2bc1bab97">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Capitalized Materials&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We capitalize the costs of certain materials that we purchase for use in manufacturing our medicines in our clinical development programs
    because until we use these materials, they have alternative future uses. We can use these materials in multiple products and, as a result, each material has future economic value independent of the development status of any single medicine. We include
    capitalized materials in other current assets in our consolidated balance sheets and expense these costs as R&amp;amp;D expenses when the materials are used. We review our capitalized materials periodically for continued alternative future use and reduce
    the carrying value of items in the period in which an impairment is identified.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2024, we reclassified capitalized costs related to materials used in our clinical development programs from inventories to other
    current assets in our consolidated balance sheets. As such, we reclassified the respective prior period amounts to conform with the current year presentation.&lt;/div&gt;
</ions:CapitalizedMaterialsPolicyPolicyTextBlock>
    <us-gaap:PropertyPlantAndEquipmentPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_cdabff15346b44629390c82abd47c849">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Property, Plant and Equipment&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which we
    determine as the following (in years):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt; &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Useful Lives&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Computer software, laboratory, manufacturing and other equipment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3 to 10&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Building, building improvements and building systems&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15 to 40&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Leasehold improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 15&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Furniture and fixtures&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 10&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived
    assets, which include property, plant and equipment, for impairment whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.&lt;/div&gt;
</us-gaap:PropertyPlantAndEquipmentPolicyTextBlock>
    <ions:PropertyPlantAndEquipmentUsefulLivesTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_ae9ad73d07bb4b9c96c8b308b9a0cddb">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which we
    determine as the following (in years):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt; &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Useful Lives&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Computer software, laboratory, manufacturing and other equipment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3 to 10&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Building, building improvements and building systems&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15 to 40&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Leasehold improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 15&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Furniture and fixtures&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 10&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</ions:PropertyPlantAndEquipmentUsefulLivesTableTextBlock>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember_RangeAxis_MinimumMember"
      id="Fact_b828ac0b40e9470bb076f1ca83c087f8">P3Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember_RangeAxis_MaximumMember"
      id="Fact_55512527b3f64093815e4719a3a9da7a">P10Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember_RangeAxis_MinimumMember"
      id="Fact_d29ce71868244871b343b50d2485de0e">P15Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember_RangeAxis_MaximumMember"
      id="Fact_dc8025be6cc74cca855f74c2367e8b3f">P40Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_LandImprovementsMember"
      id="Fact_ebc4b025a1eb42b69cfea73de031e5b1">P20Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember_RangeAxis_MinimumMember"
      id="Fact_a08cac9f5411485898c11087f1bef572">P5Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember_RangeAxis_MaximumMember"
      id="Fact_bda92ab03ee44df391ef93ce2060a192">P15Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember_RangeAxis_MinimumMember"
      id="Fact_8596a99804394834b242d29ed1c6c554">P5Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember_RangeAxis_MaximumMember"
      id="Fact_2dd75df24eaa415ab54d1ac7e3d92e45">P10Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <ions:AccruedLiabilitiesPolicyPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_c409370b54504175b0cd629ca3737408">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Accrued Liabilities&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. We estimate our liability
    for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to third-party clinical management
    costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted
    fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these costs may differ
    materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.&lt;/div&gt;
</ions:AccruedLiabilitiesPolicyPolicyTextBlock>
    <us-gaap:DebtPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_30f2fdb1a267491fb1834b1b077b624c">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Convertible Debt&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We account for each of our convertible debt instruments as a
      single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt
      issuance costs as contra-liabilities in our consolidated balance sheets at issuance and amortize them over the contractual term of the convertible debt instrument using the effective interest rate. &lt;/span&gt;The&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; balances of our convertible senior notes presented in our consolidated balance sheets represent the principal balance of each convertible debt instrument less debt issuance costs.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2024, we
    had two outstanding convertible senior notes, our 1.75%
    Notes, which mature in June 2028, and our 0% Notes, which mature in April 2026. Our 0.125% Notes matured in December 2024. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term Obligations and
      Commitments&lt;/span&gt;, for further details on our convertible senior notes.&lt;/div&gt;
</us-gaap:DebtPolicyTextBlock>
    <ions:DebtInstrumentNumberOfConvertibleNotes
      contextRef="c20241231"
      decimals="INF"
      id="Fact_10f5114021fc4f5bb04196fe30354c8a"
      unitRef="U010">2</ions:DebtInstrumentNumberOfConvertibleNotes>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember"
      decimals="4"
      id="Fact_0da40ce130a0427ca4507455e50f00de"
      unitRef="U003">0.0175</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_88cf15606ae648ba879a91ce9224095e"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_637081ace1c3467395b29f412ee7c215"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DerivativesPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_aa6c21ff1d40469fbb64ee19c123e452">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with the issuance of our 0%
    Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of
    purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not
    meet the definition of a liability using the guidance contained in ASC Topic 480; therefore, we account for the note hedges and warrants using the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Derivatives







      and Hedging &#x2013; Contracts in Entity&#x2019;s Own Equity&lt;/span&gt; accounting guidance contained in ASC Topic 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified
    in shareholders&#x2019; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our consolidated balance sheets. We reassess our ability to continue to classify any
    outstanding note hedges and warrants in shareholders&#x2019; equity at each reporting period. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term Obligations and Commitments&lt;/span&gt;, for
    further details on the call spread transactions. &lt;/div&gt;
</us-gaap:DerivativesPolicyTextBlock>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_fe2e410b891c4e8f90e9c7af0b2fd97c"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_ad09e792f7534196a47d6e0a5fba48da"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <ions:LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_d7ae37f96f1545d5a50ffc981607ee57">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Liability Related to Sale of Future Royalties&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. Under our agreement with Royalty Pharma, we record upfront payments and milestone payments we receive from the sale of future
    royalties as a liability, net of transaction costs. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term Obligations and Commitments&lt;/span&gt;, for further details on the agreement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We record royalty payments made to Royalty Pharma as a reduction of the liability or accrued interest and amortize the transaction costs
    over the estimated life of the royalty stream. We account for the associated interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the
    related product and recognizes the related revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense using our
    current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material
    change in our estimate, we will prospectively adjust the effective interest rate and the related interest expense.&lt;/div&gt;
</ions:LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock>
    <us-gaap:LesseeLeasesPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_5a1cbe260fe343ccafe9ff400e9af2db">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use
    operating lease asset and associated short- and long-term operating lease liability in our consolidated balance sheets for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term
    and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we
    will pay over the lease term.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&#160;&lt;/span&gt;We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal
    options if we conclude we are reasonably certain to exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease
    term.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information
    available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease.
    Our leases do not include material variable or contingent lease payments. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.&lt;/div&gt;
</us-gaap:LesseeLeasesPolicyTextBlock>
    <us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock
      contextRef="c20240101to20241231"
      id="Text_702601a4d67748f5a98dd7344990b6c7">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Recent Accounting Standards&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2023, the Financial Accounting Standards Board, or FASB, issued Accounting Standard Update, or ASU, 2023-07, which provides
    updated guidance on segment reporting. The guidance requires public companies to disclose significant expenses that are regularly provided to the CODM, other segment items for each reportable segment and measures of segment profit or loss used by the
    CODM for allocating resources. In addition, the updated guidance requires public companies with a single reportable segment to provide all disclosures required under ASC 280, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Segment Reporting&lt;/span&gt;, and public companies to include in interim reports all disclosures related to a reportable segment&#x2019;s profit or loss and assets that are currently required in annual reports. This update is effective for
    annual periods beginning after December 15, 2023 and interim periods beginning after December 15, 2024. The guidance is applied on a retrospective basis for all periods presented in the financial statements, unless it is impracticable. We adopted the
    annual reporting requirements in our 2024 Annual Report on Form 10-K. We expect to adopt the interim reporting requirements in our Quarterly Report on Form 10-Q in the first quarter of 2025. Refer to Note 12, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Segment Information&lt;/span&gt;, for further details on our segment information.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2023, the FASB issued ASU 2023-09, which provides updated guidance on income tax disclosures. The new guidance requires
    companies to provide additional disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions and
    unrecognized deferred tax liabilities. This update is effective for annual periods beginning after December 15, 2024. Early adoption of this guidance is permitted. The guidance may be applied on a prospective or retrospective basis. We currently plan
    to adopt this guidance in our 2025 Annual Report on Form 10-K.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2024, the FASB issued ASU 2024-03, which requires public companies to disclose disaggregated expenses for certain expenses in
    the income statement. This update is effective for annual periods beginning after December 15, 2026 and interim periods within annual periods beginning after December 15, 2027. Early adoption of this guidance is permitted. The guidance may be applied
    on a prospective or retrospective basis. We are currently assessing the impact and timing of adopting this update.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2024, the FASB issued ASU 2024-04 to clarify the guidance for determining whether to account for early settlements of
    convertible debt as induced conversions or extinguishments. This update is effective for annual periods beginning after December 15, 2025 and interim periods within those annual periods. Early adoption of this guidance is permitted. The guidance may be
    applied on a prospective or retrospective basis. We are currently assessing the impact and timing of adopting this update.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not expect any other recently issued accounting standards to have a material impact to our financial statements or disclosures.&lt;/div&gt;
</us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock>
    <us-gaap:SupplementalBalanceSheetDisclosuresTextBlock
      contextRef="c20240101to20241231"
      id="Text_49076dbe5ad448cdb9a7bcb57a3d6075">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2. Supplemental Financial Data&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Inventories&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our inventory consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -19.4pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,557&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,810&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,679&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,477&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Finished goods&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;276&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;154&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventories&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,512&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,441&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Property, Plant and Equipment&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our property, plant and equipment consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="background-color: #CCEEFF; vertical-align: bottom; white-space: nowrap; width: 76%;"&gt;
          &lt;div style="text-align: left; margin-left: 6.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Computer software, laboratory, manufacturing and other equipment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86,540&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79,885&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Building, building improvements and building systems&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,228&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,228&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Leasehold improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,375&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,276&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Furniture and fixtures&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,855&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,844&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;191,998&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;159,233&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Accumulated depreciation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(106,316&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(96,759&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;85,682&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;62,474&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,569&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,569&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 33.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#160;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;94,251&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,043&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Accrued Liabilities&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our accrued liabilities consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Clinical expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,436&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105,967&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In-licensing expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,951&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,454&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,589&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,875&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other miscellaneous expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19,462&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;29,598&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total accrued liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;108,438&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;147,894&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:SupplementalBalanceSheetDisclosuresTextBlock>
    <us-gaap:ScheduleOfInventoryCurrentTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_a9f4657750f748f0873e72b36f2a3b63">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our inventory consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -19.4pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,557&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,810&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,679&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,477&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Finished goods&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;276&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;154&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventories&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,512&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,441&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfInventoryCurrentTableTextBlock>
    <us-gaap:InventoryRawMaterials
      contextRef="c20241231"
      decimals="-3"
      id="Fact_7e65ee83c9b042398f7e6230c7b98cd0"
      unitRef="U001">5557000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20231231"
      decimals="-3"
      id="Fact_f70c7e8884224d6f9229c90589361e70"
      unitRef="U001">1810000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20241231"
      decimals="-3"
      id="Fact_666c46286abc442fbebc6baa888f870c"
      unitRef="U001">6679000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20231231"
      decimals="-3"
      id="Fact_b6b68af9767b48ce9e4195a93e54aa64"
      unitRef="U001">5477000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20241231"
      decimals="-3"
      id="Fact_2ce24e72453c4c46aabcad3d73fe6284"
      unitRef="U001">276000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20231231"
      decimals="-3"
      id="Fact_24167fa6e6d442398490541d6ad73f36"
      unitRef="U001">154000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryNet
      contextRef="c20241231"
      decimals="-3"
      id="Fact_4803a14d03d74237b17f8d63e8173b4c"
      unitRef="U001">12512000</us-gaap:InventoryNet>
    <us-gaap:InventoryNet
      contextRef="c20231231"
      decimals="-3"
      id="Fact_346da7c3659d43908f2c18156ff2131f"
      unitRef="U001">7441000</us-gaap:InventoryNet>
    <us-gaap:PropertyPlantAndEquipmentTextBlock
      contextRef="c20240101to20241231"
      id="Text_2add9cef486d4c08a940716c68c05cb1">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our property, plant and equipment consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="background-color: #CCEEFF; vertical-align: bottom; white-space: nowrap; width: 76%;"&gt;
          &lt;div style="text-align: left; margin-left: 6.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Computer software, laboratory, manufacturing and other equipment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86,540&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79,885&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Building, building improvements and building systems&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,228&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,228&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Leasehold improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,375&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,276&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Furniture and fixtures&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,855&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,844&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;191,998&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;159,233&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Accumulated depreciation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(106,316&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(96,759&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;85,682&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;62,474&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,569&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,569&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 33.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#160;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;94,251&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,043&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:PropertyPlantAndEquipmentTextBlock>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember"
      decimals="-3"
      id="Fact_3f415076adb64aefb62a6200aa09373b"
      unitRef="U001">86540000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember"
      decimals="-3"
      id="Fact_853375bcf45b4e2292895881e2f2165f"
      unitRef="U001">79885000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember"
      decimals="-3"
      id="Fact_be347fecf99442269a1147ce15f0acde"
      unitRef="U001">41228000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember"
      decimals="-3"
      id="Fact_55e9ea1cd6d04777a5fd335b1d632465"
      unitRef="U001">41228000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember"
      decimals="-3"
      id="Fact_8771d2aee3184880a9f8683acca837e9"
      unitRef="U001">54375000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember"
      decimals="-3"
      id="Fact_afa97b7033ec449abdf9f88c730430b3"
      unitRef="U001">28276000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember"
      decimals="-3"
      id="Fact_0a06832d59cb4e7b9ffef331f3c9e8f6"
      unitRef="U001">9855000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember"
      decimals="-3"
      id="Fact_91cf4808a4ff4d89b617433a31ee3716"
      unitRef="U001">9844000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember"
      decimals="-3"
      id="Fact_7f69b083e88341d0a10c7007be88479a"
      unitRef="U001">191998000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember"
      decimals="-3"
      id="Fact_3f9477a2105042be8cc52f98c29cba1b"
      unitRef="U001">159233000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment
      contextRef="c20241231"
      decimals="-3"
      id="Fact_f5a1f6ad7d4e4b6b8e9550921b213332"
      unitRef="U001">106316000</us-gaap:AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment>
    <us-gaap:AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment
      contextRef="c20231231"
      decimals="-3"
      id="Fact_be9d2cd137b9488d8e04e6515601bea3"
      unitRef="U001">96759000</us-gaap:AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment>
    <us-gaap:PropertyPlantAndEquipmentNet
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember"
      decimals="-3"
      id="Fact_4007d53a89214452be36c3718789c2f6"
      unitRef="U001">85682000</us-gaap:PropertyPlantAndEquipmentNet>
    <us-gaap:PropertyPlantAndEquipmentNet
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember"
      decimals="-3"
      id="Fact_8455ab90089d4679b0ea871acfd5ffa0"
      unitRef="U001">62474000</us-gaap:PropertyPlantAndEquipmentNet>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_LandMember"
      decimals="-3"
      id="Fact_c9348a3d1fce44199a8e4bed4478b232"
      unitRef="U001">8569000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_LandMember"
      decimals="-3"
      id="Fact_d9ffdb0b4d834bedb849aa2a434edef4"
      unitRef="U001">8569000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentNet
      contextRef="c20241231"
      decimals="-3"
      id="Fact_624e9fa15570492aa71339f6bd1dedf0"
      unitRef="U001">94251000</us-gaap:PropertyPlantAndEquipmentNet>
    <us-gaap:PropertyPlantAndEquipmentNet
      contextRef="c20231231"
      decimals="-3"
      id="Fact_90431cc0470047e4b4d48b3cd20bde96"
      unitRef="U001">71043000</us-gaap:PropertyPlantAndEquipmentNet>
    <us-gaap:ScheduleOfAccruedLiabilitiesTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_2045eb16e89646bfa0fb76a5f5050910">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our accrued liabilities consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Clinical expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,436&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105,967&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In-licensing expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,951&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,454&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,589&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,875&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other miscellaneous expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19,462&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;29,598&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total accrued liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;108,438&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;147,894&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfAccruedLiabilitiesTableTextBlock>
    <ions:AccruedClinicalDevelopmentExpenses
      contextRef="c20241231"
      decimals="-3"
      id="Fact_a67b9aa3ded9444ea6fa8750f375469c"
      unitRef="U001">77436000</ions:AccruedClinicalDevelopmentExpenses>
    <ions:AccruedClinicalDevelopmentExpenses
      contextRef="c20231231"
      decimals="-3"
      id="Fact_6080a8023b8a4a7680a671237d572043"
      unitRef="U001">105967000</ions:AccruedClinicalDevelopmentExpenses>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_97e185cf18574068bda549c444019ebd"
      unitRef="U001">7951000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_99a4ffc78cea4ea79a97e34f63ad0e36"
      unitRef="U001">7454000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_a85290633cb748aa801b0128951ad078"
      unitRef="U001">3589000</ions:AccruedCommercialExpensesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_6e4c39c15d234eb09c433b9792328307"
      unitRef="U001">4875000</ions:AccruedCommercialExpensesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_159ba94a17f648459aba5b5549ce591d"
      unitRef="U001">19462000</us-gaap:OtherAccruedLiabilitiesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_ec657cc584984d58a779e475cb9c827b"
      unitRef="U001">29598000</us-gaap:OtherAccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_c527b3021abd4093a2c21fd084cef7d4"
      unitRef="U001">108438000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_8efb348efdaa4293a28fe2308d0572ac"
      unitRef="U001">147894000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:RevenueFromContractWithCustomerTextBlock
      contextRef="c20240101to20241231"
      id="Text_8fa4a07991ac4286b221053dfdaeed02">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;3. Revenues&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;During the years ended December 31, &lt;/span&gt;2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2022, our revenues were comprised of the following (in
    thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial revenue:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;216,090&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;240,379&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;242,314&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;WAINUA royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,207&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other commercial revenue:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;TEGSEDI and WAYLIVRA revenue, net&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,189&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,913&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30,051&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,590&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,299&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30,993&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total other commercial revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,779&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;68,212&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;61,044&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293,076&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;308,591&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;303,358&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research and development revenue:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Collaborative agreement revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;332,647&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;352,657&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;207,222&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;WAINUA joint development revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79,415&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;126,399&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76,787&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total research and development revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;412,062&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;479,056&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;284,009&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 54pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;705,138&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;787,647&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;587,367&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="text-decoration: underline;"&gt;Revenue Sources&lt;/span&gt;&lt;/span&gt;&#160;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following are sources of revenue and when we typically recognize revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We earn commercial revenue primarily in the form of royalty
      payments on net sales of SPINRAZA and WAINUA. In &lt;/span&gt;2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we began earning royalties on net sales of WAINUA.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We earn commercial revenue from TEGSEDI and WAYLIVRA sales
      under our distribution agreements with &lt;/span&gt;Sobi&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. In addition, we receive royalties from&lt;/span&gt; PTC Therapeutics International Limited, or PTC, for TEGSEDI and WAYLIVRA
    sales. Refer to Note 4, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/span&gt;, for details on our commercialization partnerships with Sobi and PTC.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also recognize as commercial revenue sales milestone payments and royalties we earn under our other collaborations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In &lt;/span&gt;December 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the FDA approved TRYNGOLZA (olezarsen) in the U.S. for the treatment of familial chylomicronemia syndrome, or FCS. Our launch of TRYNGOLZA is currently underway.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Research and development revenue under collaboration agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration
    agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, R&amp;amp;D services and manufacturing services.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For R&amp;amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the
    effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period,
    relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make
    numerous estimates and may use judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Upfront payments:&lt;/span&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;When we enter into a collaboration agreement and receive an upfront payment, we record the entire upfront payment as deferred revenue if our only performance obligation is for
      R&amp;amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;amp;D services. If part or all of the upfront payment is a license fee, we recognize as revenue the portion related to the license when
      we deliver the license to our partner because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Milestone payments:&lt;/span&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We include variable consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;amp;D services in the transaction price when they are
      achieved. We include these milestone payments when they are achieved because there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include regulatory milestone payments in the
      transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting
      rules.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, when we
    achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&amp;amp;D services performance obligation and
    recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone payment to the
    transaction price.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversely, we recognize in full those milestone payments that we earn based on our partners&#x2019; activities when our partner achieves the
    milestone event and we do not have a remaining performance obligation. For example, in 2024, we earned a $10 million milestone payment from
    Biogen when the Ministry of Health, Labour and Welfare of Japan approved Biogen&#x2019;s Japanese New Drug Application filing of QALSODY, which we recognized in full because we did not have any remaining performance obligations related to this milestone
    payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;License fees:&lt;/span&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner because our partner has
      full use of the license and we do not have any additional performance obligations related to the license after delivery.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;WAINUA (Eplontersen) Collaboration with AstraZeneca&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize WAINUA for the
    treatment of transthyretin amyloidosis, or ATTR. Under the terms of the agreement, we received a $200 million upfront payment in 2021. Refer to
    Note 4, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/span&gt;, for further details on this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluated our WAINUA collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the
    co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations
    after we delivered the license to AstraZeneca.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an
    accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#x2019;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing WAINUA to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related
    to commercial and medical affairs activities as reductions of our SG&amp;amp;A expense and R&amp;amp;D expense, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Swedish Orphan Biovitrum AB (Sobi)&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, we concluded that our performance obligation is to provide
    services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global
    commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished
    goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#x2019;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.&lt;/div&gt;
</us-gaap:RevenueFromContractWithCustomerTextBlock>
    <us-gaap:DisaggregationOfRevenueTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_9914efd2504d4b07a8cc31caeee2e3b1">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;During the years ended December 31, &lt;/span&gt;2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2022, our revenues were comprised of the following (in
    thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial revenue:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;216,090&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;240,379&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;242,314&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;WAINUA royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,207&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other commercial revenue:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;TEGSEDI and WAYLIVRA revenue, net&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,189&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,913&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30,051&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,590&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,299&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30,993&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total other commercial revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,779&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;68,212&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;61,044&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293,076&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;308,591&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;303,358&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research and development revenue:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Collaborative agreement revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;332,647&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;352,657&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;207,222&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;WAINUA joint development revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79,415&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;126,399&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76,787&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total research and development revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;412,062&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;479,056&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;284,009&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 54pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;705,138&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;787,647&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;587,367&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20240101to20241231_ProductOrServiceAxis_QalsodyMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember"
      decimals="-6"
      id="Fact_4d9d2b202ef043fab4e39a96a7369340"
      unitRef="U001">10000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:UpfrontPaymentReceived
      contextRef="c20210101to20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember"
      decimals="-6"
      id="Fact_6bb92631bcb24cecb14c1db01373726d"
      unitRef="U001">200000000</ions:UpfrontPaymentReceived>
    <ions:NumberOfMaterialComponents
      contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember"
      decimals="INF"
      id="Fact_77244fc7a2e94cb79c8cbd4b24da3caa"
      unitRef="U011">4</ions:NumberOfMaterialComponents>
    <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations
      contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember"
      decimals="INF"
      id="Fact_ba2c8e8b9b084f918923e87c66222bf9"
      unitRef="U012">1</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
    <ions:RevenueFromContractWithCustomerTransactionPrice
      contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember"
      decimals="-6"
      id="Fact_7a3ad0b9fdcd4f748e4e867ab2270c0c"
      unitRef="U001">200000000</ions:RevenueFromContractWithCustomerTransactionPrice>
    <ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner
      contextRef="c20240101to20241231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember"
      decimals="2"
      id="Fact_5e87322def9b4973aefbf130af9125cb"
      unitRef="U003">0.55</ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner>
    <us-gaap:CollaborativeArrangementDisclosureTextBlock
      contextRef="c20240101to20241231"
      id="Text_80c8d3faa85543f28cd974b1bfe28318">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;4. Collaborative Arrangements and Licensing Agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;AstraZeneca&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;WAINUA (Eplontersen) Collaboration&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for
    the treatment of ATTR. The FDA and Health Canada approved eplontersen with the brand name, WAINUA, for hereditary ATTR, or ATTRv-PN, while the Medicines and Healthcare products Regulatory Agency, or MHRA, approved WAINUA for ATTRv-PN in the United
    Kingdom, or UK, as WAINZUA. Under the agreement, we are jointly developing WAINUA with AstraZeneca worldwide for ATTRv-PN and ATTR cardiomyopathy, or ATTR-CM. We are jointly commercializing WAINUA with AstraZeneca in the U.S. We granted AstraZeneca
    exclusive rights to commercialize WAINUA outside the U.S.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Over the term of the collaboration, we are eligible to
      receive up to $&lt;/span&gt;3.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion, which is comprised of a $&lt;/span&gt;200&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment, up to $&lt;/span&gt;485&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in development and approval milestone payments and up to $&lt;/span&gt;2.9&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion in sales milestone payments. The agreement includes
      territory-specific development, commercial and medical affairs cost-sharing provisions. In addition, we are eligible to receive up to mid-&lt;/span&gt;20 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.S. From inception through &lt;/span&gt;December 31, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we have received more than $&lt;/span&gt;465&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in payments under this collaboration. We will achieve the next payment of $&lt;/span&gt;200&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million or $&lt;/span&gt;115&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upon regulatory approval of WAINUA for ATTR-CM in the U.S. or Europe, respectively, under
      this collaboration.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. As a result, we began earning
    royalties from WAINUA sales, which we recognize as commercial revenue in our consolidated statements of operations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluated our WAINUA collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca will perform, (iii) the co-commercialization
    activities that we and AstraZeneca will perform and (iv) the co-medical affairs activities that we and AstraZeneca will perform.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received in 2021. In 2023, we earned a $20 million license fee payment when we licensed rights to Latin America for WAINUA to AstraZeneca. We recognized these payments in full because we did not have any remaining performance obligations after we delivered the
    licenses to AstraZeneca.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration. AstraZeneca is currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we recognize as revenue the 55 percent of cost-share funding AstraZeneca is responsible for in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing WAINUA to market outside the U.S., we recognize cost-share funding we receive from AstraZeneca related to these activities as a reduction of
    our commercial and medical affairs expenses. In the fourth quarter of 2024, we earned a $30 million milestone payment from AstraZeneca when the
    MHRA approved WAINZUA for ATTRv-PN in the UK. We recognized this milestone payment in full as joint development revenue because we did not have any remaining performance obligations related to the milestone payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Cardiovascular, Renal and Metabolic Collaboration&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In addition to our collaboration for WAINUA, we have a collaboration with AstraZeneca focused on discovering and developing treatments for
    cardiovascular, renal and metabolic diseases, which we formed in 2015. In December 2024, we amended this collaboration agreement with AstraZeneca. The amendment changed future potential milestone payments and royalties we could receive under the
    collaboration. We determined there were no changes that would require adjustments to revenue we previously recognized because we had no ongoing performance obligations under the agreement. Under our collaboration, AstraZeneca has licensed multiple
    medicines from us. AstraZeneca is responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed from us.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive up to $4.3 billion, which is comprised of a $65 million upfront payment, up to $175 million in license fees, up to $514 million
    in development milestone payments, up to $863 million in regulatory milestone payments and up to $2.8 billion in sales milestone payments. In addition, we are eligible to receive tiered royalties up to 10 percent on net sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. From inception through December 31, 2024, we have received more than $340
    million in payments under this collaboration. We will achieve the next payment of up to $30 million if AstraZeneca advances a medicine under this
    collaboration&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for AstraZeneca. We determined the transaction price to be the $65
    million upfront payment we received and we allocated it to our single performance obligation. We recognized revenue for our R&amp;amp;D services performance obligation as we performed services based on our effort to satisfy this performance obligation
    relative to our total effort expected to satisfy our performance obligation. We&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; completed our performance obligation in&lt;/span&gt; 2021. As we achieved milestone payments for our
    R&amp;amp;D services, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation. From inception through the completion of our performance obligation, we have included $90 million in payments in the transaction price for our R&amp;amp;D services performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;amp;D services performance
    obligation. We recognized each of these payments in full in the respective period we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. For example, in the fourth quarter
    of 2024, we earned a $25 million payment when AstraZeneca licensed a compound from us. We recognized this payment in full in 2024 because we did
    not have any remaining performance obligations after we delivered the license to AstraZeneca.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with AstraZeneca&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;129,759&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;202,236&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79,160&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have any
    deferred revenue from our relationship with AstraZeneca at December 31, 2024 and 2023.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Biogen&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Marketed Medicines&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;SPINRAZA&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In 2012, we entered into a collaboration agreement with
      Biogen to develop and commercialize SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA.&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through &lt;/span&gt;December 31, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we received more than $&lt;/span&gt;2.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion in total payments under this collaboration, including approximately
      $&lt;/span&gt;1.8&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion from SPINRAZA royalties and more than $&lt;/span&gt;425&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million from R&amp;amp;D revenue. We are receiving tiered royalties ranging
      from &lt;/span&gt;11 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to &lt;/span&gt;15 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; on net sales of SPINRAZA. We have exclusive in-licensed patents
      related to SPINRAZA from Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on net sales of SPINRAZA. Biogen is responsible for all
      global development, regulatory and commercialization activities and costs for SPINRAZA. We completed our performance obligations under this collaboration in 2016&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2023, we entered into a royalty purchase agreement with Royalty Pharma in which Royalty Pharma receives 25 percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to 45 percent of royalty payments in 2028, on up to $1.5 billion in annual
    sales. Royalty Pharma&#x2019;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $475
    million or $550 million, depending on the timing and occurrence of the U.S. Food and Drug Administration, or FDA, approval of pelacarsen, which
    Novartis is developing. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term Obligations and Commitments&lt;/span&gt;, for further discussion of this agreement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;QALSODY&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2018, Biogen exercised its option to license QALSODY, our medicine that received accelerated approval from the FDA in April 2023 and
    marketing authorization under exceptional circumstances from the European Medicines Agency, or EMA, in May 2024 for the treatment of adult patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS. As a result, Biogen is
    responsible for global development, regulatory and commercialization activities and costs for QALSODY. Biogen is also evaluating QALSODY as a potential treatment for presymptomatic SOD1-ALS patients in the ongoing ATLAS study. From inception through December 31, 2024, we received more than $110
    million in total payments under this collaboration, including approximately $3 million from QALSODY royalties and $108 million from R&amp;amp;D revenue. We are receiving tiered royalties ranging from 11 percent to 15 percent on net sales of QALSODY. We completed our
    performance obligations under this collaboration in 2020.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;New Antisense Medicines for the Treatment of SMA&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In 2017, we entered into a collaboration agreement with
      Biogen to &lt;/span&gt;identify &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;new antisense medicines for the treatment of SMA&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;At the commencement of this collaboration, we received a &lt;/span&gt;$25 million&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; upfront payment from Biogen. In &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2021&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, Biogen exercised its option to license ION&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;306&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, a drug we discovered under this collaboration, for which &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;we earned a $&lt;/span&gt;60&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million license fee payment. We recognized this payment as revenue in full because&lt;/span&gt; Biogen had full use of the license without any continuing involvement from us. Biogen is solely responsible for the costs and
    expenses related to the development, manufacturing and potential future commercialization of ION306 following the option exercise. We do not have any remaining performance obligations under this collaboration. &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We will receive development and regulatory milestone payments from Biogen if new medicines, including ION&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;306&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, advance towards marketing approval.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive up to $555 million if Biogen advances ION306, which is comprised of up to $45
    million in development milestone payments, up to $110 million in regulatory milestone payments and up to $400 million in sales milestone payments. In addition, we are eligible to receive tiered royalties &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;from the mid-teens to &lt;/span&gt;mid-20 percent range &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;on net sales from any product that Biogen successfully commercializes under this collaboration.&lt;/span&gt; From inception through December 31, 2024, we received $85 million in payments under this
    collaboration. We will achieve the next payment of up to $45 million &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;if Biogen initiates a Phase 3 trial under this collaboration.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Neurology Collaborations&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have multiple collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders,
    including our 2018 and 2012 neurology collaborations. Under these collaborations, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for certain neurological diseases and the option to license certain medicines
    resulting from these collaborations. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our 2018 neurology collaboration, we are currently advancing multiple programs. For each medicine under this collaboration, we are
    eligible to receive &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;up to $&lt;/span&gt;270&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, which is comprised of a $&lt;/span&gt;15&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million license fee, up to $&lt;/span&gt;105&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in development milestone payments and up to $&lt;/span&gt;150&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in regulatory milestone payments&lt;/span&gt;. In addition, we are eligible to receive tiered royalties up to
    the 20 percent range on net sales from any product that Biogen successfully commercializes under this collaboration. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through &lt;/span&gt;December 31, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we have received nearly $&lt;/span&gt;1.1&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion in payments under this collaboration, including payments to purchase our stock. &lt;/span&gt;We will achieve the next payment of up to $15 million if Biogen licenses a medicine under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of our 2018 neurology collaboration, we determined our transaction price to be $552 million, comprised of $375 million from the upfront payment and $177 million for the premium paid by Biogen for its purchase of our common stock. We allocated the transaction price to our single performance obligation,
    which was to perform R&amp;amp;D services for Biogen. From inception through December 31, 2024, we have included $623 million in upfront and milestone payments in the transaction price for our R&amp;amp;D services performance obligation. We recognize revenue for our R&amp;amp;D
    services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance
    obligation at the end of the contractual term in June 2028.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our 2012 neurology collaboration, Biogen exercised its option to license IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;, an investigational RNA-targeted
    medicine for the potential treatment of Alzheimer&#x2019;s disease, or AD, in 2019. As a result, Biogen is responsible for global development, regulatory and commercialization activities and costs for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;. We are eligible to receive up to
    $185 million for the IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; program, which is comprised of a license fee of $45 million, up to $10 million in development milestone payments and up to
    $130 million in regulatory milestone payments, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. In addition, we are eligible to
    receive tiered royalties up to the mid-teens on net sales of any medicines resulting from the IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; program. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through &lt;/span&gt;December 31, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we have received more than $&lt;/span&gt;230&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in payments under this collaboration. &lt;/span&gt;We will achieve the
    next payment of $25 million if Biogen advances MAPT&lt;sub&gt;Rx&lt;/sub&gt; into Phase 3 development under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of our 2012 neurology collaboration, we identified two separate performance obligations as our development work for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; and ION582. We completed our R&amp;amp;D services performance obligations for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;
    and ION582 in 2022 and 2024, respectively. From inception through the completion of our performance obligations, we have included $57 million in
    the transaction price for our IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; development performance obligation. From inception through the completion of our performance obligations, we have included $68 million in milestone payments in the transaction price for our ION582 development performance obligation. We recognized revenue for our R&amp;amp;D services performance obligations
    as we performed services based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the second quarter of 2024, Biogen&#x2019;s option to license ION582, an investigational antisense medicine for the potential treatment of
    Angelman syndrome, or AS, expired unexercised. As a result, we recognized $30 million of R&amp;amp;D revenue from previously deferred milestone
    payments related to the ION582 study because we did not have any remaining performance obligations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Biogen&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;368,058&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;350,146&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;366,696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;44&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;62&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our &lt;/span&gt;consolidated balance sheets at December 31&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred
      revenue of $&lt;/span&gt;211.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;307.4&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, respectively, from our relationship with Biogen.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;GSK&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2010, we entered into a collaboration with GSK using our antisense drug discovery platform to discover and develop new medicines
    against targets for serious and rare diseases, including infectious diseases. Upon initiating the collaboration, we received an upfront payment of $35
    million. Under our collaboration, GSK is developing bepirovirsen for the treatment of chronic hepatitis B virus infection, or HBV, infection. In 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global
    development, regulatory and commercialization activities and costs for the HBV program.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive nearly $260 million, which is comprised of a $25 million license fee, up to $42.5 million in development milestone payments, up to $120
    million in regulatory milestone payments and up to $70 million in sales milestone payments if GSK successfully develops and commercializes
    bepirovirsen. In addition, we are eligible to receive tiered royalties up to the low-teens on net sales of bepirovirsen. From inception through December 31, 2024, we have received more than $105 million in an upfront payment and payments related to the HBV program.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We completed our R&amp;amp;D services performance obligations in 2015. Therefore, we do not have any remaining performance obligations under
    our collaboration with GSK. However, we can still earn additional payments and royalties as GSK advances the HBV program.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; In 2023, we earned a $&lt;/span&gt;15&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone payment when GSK initiated a Phase 3 program of
      bepirovirsen. We recognized this milestone payment as R&amp;amp;D revenue in full in 2023 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next payment of $&lt;/span&gt;15&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million if the FDA accepts an NDA filing of bepirovirsen for review.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with GSK (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with GSK&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,000&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have any
    deferred revenue from our relationship with GSK at December 31, 2024 and 2023.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Novartis&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Pelacarsen Collaboration&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In 2017, we initiated a collaboration with Novartis to
      develop and commercialize pelacarsen.&lt;/span&gt; Novartis is responsible for conducting and funding development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study that Novartis initiated in 2019.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive up to $900 million, which is comprised of a $75 million upfront payment, a $150 million license fee, a $25 million
    development milestone payment, up to $290 million in regulatory milestone payments and up to $360 million in sales milestone payments. We are also eligible to receive tiered royalties in the mid-teens to low 20 percent range on net sales of pelacarsen. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through &lt;/span&gt;December 31, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we have received more than $&lt;/span&gt;275&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in payments under this collaboration. We&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; will achieve the next payment of $&lt;/span&gt;50&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million if the FDA accepts an NDA filing for pelacarsen.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;At the commencement of this collaboration, &lt;/span&gt;we
    determined our transaction price to be $108.4 million, comprised of the $75 million from the upfront payment, $28.4 million for the premium paid
    by Novartis for its purchase of our common stock and $5.0 million for the potential premium Novartis would have paid if they purchased our common
    stock in the future. We &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;identified &lt;/span&gt;four&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; separate performance obligations as the R&amp;amp;D services and API for pelacarsen and olezarsen. We recognized revenue for our R&amp;amp;D services performance obligations as we
      performed services &lt;/span&gt;based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;We
    completed our R&amp;amp;D services performance obligations for olezarsen and pelacarsen&lt;sub&gt;&#160;&lt;/sub&gt;in 2019. As such, we recognized all revenue we allocated to the olezarsen and pelacarsen&lt;sub&gt;&#160;&lt;/sub&gt;R&amp;amp;D services as of the end of 2019. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through the completion of our performance obligations, we have included $&lt;/span&gt;104&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in payments in the transaction price for our R&amp;amp;D services performance obligations under this collaboration.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As described in the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Biogen SPINRAZA&lt;/span&gt;
    section above, in 2023, we entered into a royalty purchase agreement with Royalty Pharma. Under the agreement, in addition to a minority interest in SPINRAZA royalties, Royalty Pharma will receive 25 percent of any future royalty payments on pelacarsen. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term
      Obligations and Commitments&lt;/span&gt;, for further discussion of this agreement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;New Medicine for the Treatment of Lp(a)-Driven Cardiovascular Disease&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In August 2023, we entered into a collaboration and license agreement with Novartis for the discovery, development and commercialization
    of a novel medicine for patients with Lp(a)-driven cardiovascular disease, or lipoprotein(a)-driven CVD. Novartis is solely responsible for the development, manufacturing and potential commercialization of the next generation Lp(a) therapy.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive up to $730 million, which is comprised of a $60 million upfront payment, up to $155 million in development milestone payments, up to $105
    million in regulatory milestone payments and up to $410 million in sales milestone payments. In addition, we are eligible to receive tiered
    royalties ranging from 10 percent to 20 percent
    on net sales. From inception through December 31, 2024, we have received more than $65 million from payments under this collaboration. We will achieve the next payment of $10
    million if Novartis advances a medicine under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;At the commencement of this collaboration, we identified &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; performance obligation, which was to perform R&amp;amp;D services for Novartis.
    &lt;/span&gt;We recognized revenue for our R&amp;amp;D services performance obligation as we performed services based on our effort to satisfy this performance obligation relative to our total effort expected to satisfy our performance obligation. We&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; completed our performance obligation in&lt;/span&gt; the third quarter of 2024. As we achieved milestone payments for our R&amp;amp;D services, we included these amounts in our transaction
    price for our R&amp;amp;D services performance obligation.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; From inception through the completion of our performance obligation, we have included $&lt;/span&gt;65&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in upfront and milestone payments in the transaction price for our
      R&amp;amp;D services performance obligation under this collaboration.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Novartis (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Novartis&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;37,762&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30,194&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;237&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less than 1%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our consolidated balance sheets at December 31, 2024 and 2023 included deferred revenue of $4.2 million and $30.0 million, respectively, from our relationship with Novartis.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Roche&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Sefaxersen
      (IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;) for Complement-Mediated Diseases&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2018, we entered into a collaboration agreement with Roche to&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; develop sefaxersen (IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;) for the treatment of complement-mediated diseases, including immunoglobulin A nephropathy, or IgAN, and geographic atrophy, or GA. In April 2023, Roche initiated a
    Phase 3 study of sefaxersen in patients with IgAN.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;After positive data from a Phase 2 clinical study in patients
      with IgAN, &lt;/span&gt;Roche&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; licensed &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;sefaxersen&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2022&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for $&lt;/span&gt;35&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. As a result, Roche is responsible for global development, regulatory and commercialization activities, and costs for sefaxersen. In 2022, we amended our sefaxersen
      collaboration agreement with Roche. The amendment changed future potential milestone payments we could receive under the collaboration. We determined there were no changes that would require adjustments to revenue we previously recognized.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In &lt;/span&gt;July 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, Roche discontinued development of &lt;/span&gt;sefaxersen&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of GA, following the completion of the Phase &lt;/span&gt;2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; study, which showed a favorable safety profile and target engagement, but insufficient efficacy to advance into Phase &lt;/span&gt;3&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; development.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Over the term of the &lt;/span&gt;sefaxersen &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;collaboration for the treatment of IgAN, we are eligible to receive up to $&lt;/span&gt;430&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, which is comprised of a $&lt;/span&gt;35&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million license fee, up to $&lt;/span&gt;25&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in development milestone payments, up to $&lt;/span&gt;90&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in regulatory milestone payments and up to $&lt;/span&gt;280&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in sales milestone payments. In addition, we are also eligible to receive tiered royalties from the high teens to &lt;/span&gt;20 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; on net sales.&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;From inception
    through December 31, 2024, we have received more than $140 million in payments under this collaboration. &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We will achieve the next payment of $&lt;/span&gt;23.5&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million if Roche advances sefaxersen for the
      treatment of IgAN under this collaboration.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Roche. We recognized revenue for our R&amp;amp;D services performance obligation as we performed services based on our effort to satisfy this performance
    obligation relative to our total effort expected to satisfy our performance obligation. We&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; completed our performance obligation in&lt;/span&gt; the fourth quarter of 2024. As we
    achieved milestone payments for our R&amp;amp;D services, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation. From inception through the completion of our performance obligation, we have included $97 million in upfront and milestone payments in the transaction price for our R&amp;amp;D services performance obligation under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Huntington&#x2019;s Disease&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2013, we entered into an agreement with Hoffmann-La Roche Inc and F. Hoffmann-La Roche Ltd, collectively Roche, to develop treatments
      for Huntington&#x2019;s disease, or HD, based on our antisense technology. Under the agreement, we discovered and developed tominersen, an investigational medicine targeting HTT protein. We developed tominersen through completion of our Phase 1/2 clinical
      study in people with early-stage HD. In 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. As a result, Roche is responsible for all global development, regulatory and commercialization activities and
      costs for tominersen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive up to $395 million, which is comprised of a $30 million upfront payment, a $45 million license fee, up to $70 million in
    development milestone payments, up to $170 million in regulatory milestone payments and up to $80 million in sales milestone payments as tominersen advances. In addition, we are eligible to receive up to $136.5 million in milestone payments for each additional medicine successfully developed. We are also eligible to receive tiered royalties up to the mid-teens on net sales of any
    product resulting from this collaboration. From inception through December 31, 2024, we have received more than $150 million in payments under this collaboration. We will achieve the next payment of $17.5 million if Roche advances a medicine under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Roche. We determined the transaction price to be the $30
    million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;amp;D services, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation.
    We recognized revenue for our R&amp;amp;D services performance obligation over our period of performance, which ended in 2017.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;amp;D services performance
    obligation. We recognized each of these payments in full in the respective period in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In 2021, Roche decided to
    discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest HD based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded independent data monitoring committee, or iDMC.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2023, Roche initiated the Phase 2, GENERATION HD2, study of tominersen in patients with prodromal or early manifest HD. Roche is
    focusing on early-stage and younger patients based on the post-hoc analyses from the GENERATION HD1 study that suggested tominersen may benefit these patient groups. We do not have any remaining performance obligations related to tominersen under this
    collaboration with Roche; however, we can still earn additional payments and royalties as Roche advances tominersen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;RNA-Targeting Medicines for Alzheimer&#x2019;s Disease and Huntington&#x2019;s Disease&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In September 2023, we entered into an agreement with Roche to develop two undisclosed early-stage programs for RNA-targeting investigational medicines for the treatment of AD and HD. Under the agreement, we are responsible for advancing the two programs through preclinical studies and Roche is responsible for clinical development, manufacturing and commercialization of the medicines if they
    receive regulatory approval.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive up to $625 million, which is comprised of a $60 million upfront payment, up to $167 million in development milestone payments and up to $398
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales. From inception through December 31, 2024, we have received more than $60 million in payments under this collaboration. We will achieve the next payment of $7.5 million if we advance a medicine under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We identified two performance
    obligations under this new agreement, comprised of R&amp;amp;D services for each of the two separate programs. We determined the transaction price
    to be the $60 million upfront payment we received in the fourth quarter 2023. We allocated the transaction price based on the estimated
    stand-alone selling price of each performance obligation as follows:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$45 million for the R&amp;amp;D services for the investigational
            medicine for AD; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/span&gt;15&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million for the R&amp;amp;D services for t&lt;/span&gt;he investigational medicine for HD.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are recognizing revenue for our R&amp;amp;D services
      performance obligations as we perform services based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations. &lt;/span&gt;We&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; completed our performance obligation for the investigational medicine for AD in June 2024. We currently estimate we will satisfy our performance obligation for the investigational medicine HD at the end of the research term of
      July 2025.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Roche (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Roche&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,871&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,838&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;67,202&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our &lt;/span&gt;consolidated balance sheets at December 31&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred
      revenue of $&lt;/span&gt;7.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;36.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, respectively, from our relationship with Roche.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Commercialization Partnerships&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Otsuka&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2023, we entered into an agreement with Otsuka Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe.
    In the second quarter of 2024, we expanded the agreement to include commercialization rights for donidalorsen in the Asia-Pacific region. As a result, we received a $20 million upfront payment from Otsuka. We are responsible for the ongoing development of donidalorsen. We retained the rights to commercialize donidalorsen in the U.S. and in the rest of the world, assuming regulatory
    approval.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of this collaboration, we are eligible to receive up to $290 million, which is comprised of $85 million in upfront payments, up to
    $65 million in regulatory milestone payments and up to $140 million in sales milestone payments. In addition, we are eligible to receive tiered royalties up to 30 percent
    on net sales. In the fourth quarter of 2024, we earned a $15 million milestone payment from Otsuka when the EMA accepted our Marketing
    Authorization Application, or MAA, filing for donidalorsen in the European Union, or EU. We will achieve the next payment of $15 million if the
    European Commission approves donidalorsen under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We identified two performance
    obligations under this agreement, comprised of our license of donidalorsen to Otsuka and R&amp;amp;D services for donidalorsen. We determined the transaction price to be $85 million, comprised of the following:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$65 million from the upfront payment we received in 2023; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$20 million from the upfront payment we received in 2024.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$73.5 million for the license of donidalorsen; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$11.5 million for the R&amp;amp;D services for donidalorsen.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are recognizing revenue for our R&amp;amp;D services performance obligation as we perform services based on our effort to satisfy our
    performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligations in March 2026.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2024, we entered into an agreement with Otsuka to commercialize ulefnersen worldwide. We are responsible for the ongoing
    development of ulefnersen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From inception through December 31, 2024,
    we have received more than $95 million in payments under these collaborations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the year ended December 31, 2024, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amount):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Otsuka&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46,856&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,480&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our &lt;/span&gt;consolidated balance sheets at December 31&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred
      revenue of $&lt;/span&gt;6.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;8.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, respectively, from our relationship with Otsuka.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;PTC Therapeutics&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In 2018, we entered into an exclusive license agreement with
      PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries. Under the license agreement, we are eligible to receive royalties from PTC in the mid-&lt;/span&gt;20 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; range on net sales for each medicine. &lt;/span&gt;In December 2021 and September 2023, we
    started receiving royalties from PTC for TEGSEDI and WAYLIVRA sales, respectively&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Swedish Orphan Biovitrum AB (Sobi)&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In 2021, we began commercializing TEGSEDI and WAYLIVRA in
      Europe and TEGSEDI in North America through distribution agreements with Sobi. &lt;/span&gt;Under our distribution agreements, Sobi is responsible for commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. We are
    responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. Under our agreements with Sobi, Sobi does not generally have a right of return. We recognize as revenue the price Sobi
    pays us for the inventory when we deliver the finished goods inventory to Sobi. In addition, we earn a distribution fee on net sales from Sobi for each medicine.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2023, our distribution agreement for TEGSEDI in North America was terminated and Sobi began transitioning responsibilities to
    us. Following the transition, we discontinued TEGSEDI in North America in 2024. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;During the years ended December 31, 2024, 2023 and 2022, we earned nominal revenue from our
      distribution agreement with Sobi for TEGSEDI in North America.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Technology Enhancement Collaborations&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Bicycle Therapeutics&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2020, we entered into a collaboration agreement with Bicycle and &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;obtained an option to license its peptide technology that we expect can expand our LICA platform to target both skeletal and cardiac muscle, and potentially deliver medicines across the blood brain barrier&lt;/span&gt;. In 2021, we paid $42 million when we exercised our option to license Bicycle&#x2019;s technology, which included an equity investment in Bicycle. As part of our stock purchase, we
    entered into a lockup agreement with Bicycle that restricted our ability to trade our Bicycle shares for one year. In 2021, we recorded a $7.2 million equity investment for the shares we received in Bicycle. We recognized the remaining $34.8 million as R&amp;amp;D expense in 2021. W&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;e will pay Bicycle milestone payments and royalties that are
      contingent on the achievement of certain development, regulatory and sales events.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Metagenomi&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2022, we entered into a collaboration and license agreement with Metagenomi to research, develop and commercialize investigational
    medicines for up to four initial genetic targets, and, upon the achievement of certain development milestones, four additional genetic targets using gene editing technologies. As a result, we paid $80 million to license Metagenomi&#x2019;s technologies and will pay Metagenomi certain fees for the selection of genetic targets. We recorded the $80 million payment as R&amp;amp;D expense in 2022 upon receiving a license from Metagenomi for intellectual property that is in research with no current alternate use. In addition, we
    will pay Metagenomi milestone payments and royalties that are contingent on the achievement of certain development, regulatory and sales events. We will also reimburse Metagenomi for certain of its costs in conducting its research and drug discovery
    activities under the collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Other Agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Alnylam Pharmaceuticals, Inc.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under the terms of our agreement with Alnylam, we co-exclusively (with ourselves) licensed to Alnylam our patent estate relating to
      antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics, with Alnylam having the exclusive right to grant platform sublicenses for double-stranded RNAi. In exchange for such rights, we are eligible to earn
      a technology access fee, participate in fees from Alnylam&#x2019;s partnering programs and earn future milestone and royalty payments from Alnylam. We retained exclusive rights to our patents for single-stranded antisense therapeutics and for a limited
      number of double-stranded RNAi therapeutic targets and all rights to single-stranded RNAi, or ssRNAi, therapeutics. In turn, Alnylam nonexclusively licensed to us its patent estate relating to antisense motifs and mechanisms and oligonucleotide
      chemistry to research, develop and commercialize single-stranded antisense therapeutics, ssRNAi therapeutics, and to research double-stranded RNAi compounds. We also received a license to develop and commercialize double-stranded RNAi therapeutics
      targeting a limited number of therapeutic targets on a nonexclusive basis. Additionally, in 2015, we and Alnylam entered into an alliance in which we cross-licensed intellectual property. Under this alliance, we and Alnylam each obtained exclusive
      license rights to four therapeutic programs. Alnylam granted us an exclusive, royalty-bearing license to its chemistry, RNA targeting
      mechanism and target-specific intellectual property for oligonucleotides against four targets, including FXI and Apo(a) and two other targets. In exchange, we granted Alnylam an exclusive, royalty-bearing license to our chemistry, RNA targeting mechanism and target-specific
      intellectual property for oligonucleotides against four other targets. Alnylam also granted us a royalty-bearing, non-exclusive license to new
      platform technology arising from May 2014 through April 2019 for single-stranded antisense therapeutics. In turn, we granted Alnylam a royalty-bearing, non-exclusive license to new platform technology arising from May 2014 through April 2019 for
      double-stranded RNAi therapeutics.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022, we earned the following revenue from our relationship with Alnylam (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Alnylam&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,110&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,426&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,389&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have any
    deferred revenue from our relationship with Alnylam at December 31, 2024 and 2023.&lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with AstraZeneca&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;129,759&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;202,236&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79,160&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Biogen&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;368,058&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;350,146&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;366,696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;44&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;62&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with GSK (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with GSK&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,000&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Novartis (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Novartis&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;37,762&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30,194&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;237&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less than 1%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022,
    we earned the following revenue from our relationship with Roche (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Roche&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,871&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,838&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;67,202&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the year ended December 31, 2024, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amount):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Otsuka&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46,856&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,480&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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      id="Fact_f54d6f5ead044550b599ce90b22d6d17"
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      decimals="INF"
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    <ions:NumberOfTherapeuticPrograms
      contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember"
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      id="Fact_b59f89497d794a21b1c2df7b377e99c3"
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      decimals="INF"
      id="Fact_c487e303480e4ab0959ebfea8f93a143"
      unitRef="U014">2</ions:NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement>
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      contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember"
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      id="Fact_a45941bb66ed4a98a86c4ba3cf2c4f42"
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    <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock
      contextRef="c20240101to20241231_TypeOfArrangementAxis_AlnylamPharmaceuticalsIncMember"
      id="Text_0f88f578e1cc4bc5928904be72a89aac">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024, 2023 and 2022, we earned the following revenue from our relationship with Alnylam (in thousands, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Alnylam&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,110&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,426&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,389&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20240101to20241231_TypeOfArrangementAxis_AlnylamCollaborationMember"
      decimals="-3"
      id="Fact_45285d7fd8354da4a078a4a11aba04ee"
      unitRef="U001">8110000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20230101to20231231_TypeOfArrangementAxis_AlnylamCollaborationMember"
      decimals="-3"
      id="Fact_234485bc14344d888b7bed969bbbb34c"
      unitRef="U001">28426000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20221231_TypeOfArrangementAxis_AlnylamCollaborationMember"
      decimals="-3"
      id="Fact_bce450e4b0344107ac0e55460c018791"
      unitRef="U001">21389000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20240101to20241231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AlnylamCollaborationMember"
      decimals="2"
      id="Fact_2cfe3b7062dc4a9cb5ee360d01476480"
      unitRef="U003">0.01</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AlnylamCollaborationMember"
      decimals="2"
      id="Fact_ab0a985934234f8bb07ff855cb4f906d"
      unitRef="U003">0.04</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AlnylamCollaborationMember"
      decimals="2"
      id="Fact_bd1c6a81db934c3e9265b1322ef276f8"
      unitRef="U003">0.04</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20231231_TypeOfArrangementAxis_AlnylamCollaborationMember"
      decimals="-6"
      id="Fact_87589be5c6de472fa7c2f37215199412"
      unitRef="U001">0</us-gaap:ContractWithCustomerLiability>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20241231_TypeOfArrangementAxis_AlnylamCollaborationMember"
      decimals="-6"
      id="Fact_12c9599416c543e7890f0ee3f45418ed"
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    <us-gaap:InvestmentTextBlock
      contextRef="c20240101to20241231"
      id="Text_9571e0c61df44815a452af9dc71349ef">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;5. Investments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2024:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;One year&lt;/span&gt;
            or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;one year&lt;/span&gt;
            but within &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;
            but within &lt;span style="text-indent: 0pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30"&gt;three and a half years&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As illustrated above, at December 31, 2024,
    93 percent of our available-for-sale securities had a maturity of less than two years.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these
    securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We invest in debt securities with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp;amp;
    Poor&#x2019;s, Moody&#x2019;s or Fitch, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;At December 31, 2024, we had an ownership interest of less than 20 percent &lt;/span&gt;in seven
    private companies and three public companies with which we conduct business&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following is a summary of our investments (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amortized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt; Cost&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;593,810&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;487&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(240&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;594,057&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;143,647&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;287&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;143,895&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;657,285&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;825&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(120&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;657,990&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,516&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,524&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,402,258&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,607&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(399&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,403,466&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;439,561&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;723&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,275&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;438,009&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,255&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(289&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,103&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;149,086&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;124&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(476&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;148,734&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;698&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;654,600&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;984&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,042&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;652,542&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,056,858&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,591&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,441&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,056,008&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,660&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Privately held equity securities included in deposits and other assets (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,115&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,001&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,093&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;35,012&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,027&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13,753&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46,286&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,091,870&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,618&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(17,194&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,102,294&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amortized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt; Cost&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;559,967&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;157&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,625&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;557,499&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;224,711&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(611&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;224,164&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;513,784&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;152&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,889&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;512,047&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,757&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(113&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,686&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,316,219&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;415&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,238&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,311,396&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;243,151&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,270&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(692&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;243,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;110,138&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;547&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;110,664&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;294,873&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,239&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(480&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;295,632&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,466&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,469&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;651,628&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,063&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,197&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;653,494&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,967,847&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,478&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,435&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,964,890&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;236&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,832&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,301&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Privately held equity securities included in deposits and other assets (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,115&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,001&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,125&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42,991&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;35,012&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,237&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,957&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49,292&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,002,859&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,715&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(17,392&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,014,182&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Includes investments classified as cash equivalents in our consolidated
            balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our publicly traded equity securities are included in other current
            assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2024, we recorded a $1.0 million net &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;unrealized loss in our consolidated statement of
              operations related to changes in the fair value of our investments in publicly traded companies.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at&lt;/span&gt; cost minus impairments, plus or minus changes resulting from observable price changes in
            orderly transactions for the identical or similar investment of the same issuer, which are Level 3 inputs. In the year ended December 31, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we recorded a $&lt;/span&gt;2.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million net unrealized loss in our consolidated statements of operations related to observable price changes of our investments in privately held companies.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following is a summary of our investments we considered to be temporarily impaired at&#160;&lt;/span&gt;December 31, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;(in thousands, except for number of investments):&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Less than 12 Months of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;More than 12 Months of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Temporary&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Investments&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;274&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;488,949&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,463&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,713&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(52&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;516,662&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,515&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;67,854&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(328&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;67,854&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(328&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;38&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;252,926&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(503&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,173&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(93&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;277,099&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(596&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%;"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;643&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;129&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;772&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;346&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;811,068&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,296&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52,015&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(145&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;863,083&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,441&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates
    since purchase rather than underlying credit deterioration for any of the issuers. We believe it is more likely than not that we will be able to hold our debt securities with declines in value to maturity. Therefore, we intend to hold these securities
    to maturity and anticipate full recovery of our debt securities&#x2019; amortized cost basis at maturity.&lt;/div&gt;
</us-gaap:InvestmentTextBlock>
    <us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_df6d78f5b0db4f2293f255a3abc4674a">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2024:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;One year&lt;/span&gt;
            or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;one year&lt;/span&gt;
            but within &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;
            but within &lt;span style="text-indent: 0pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30"&gt;three and a half years&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following is a summary of our investments (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amortized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt; Cost&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;593,810&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;487&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(240&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;594,057&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;143,647&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;287&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;143,895&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;657,285&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;825&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(120&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;657,990&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,516&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,524&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,402,258&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,607&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(399&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,403,466&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;439,561&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;723&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,275&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;438,009&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,255&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(289&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,103&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;149,086&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;124&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(476&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;148,734&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;698&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;654,600&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;984&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,042&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;652,542&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,056,858&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,591&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,441&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,056,008&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,660&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Privately held equity securities included in deposits and other assets (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,115&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,001&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,093&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;35,012&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,027&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13,753&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46,286&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,091,870&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,618&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(17,194&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,102,294&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amortized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt; Cost&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;559,967&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;157&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,625&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;557,499&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;224,711&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(611&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;224,164&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;513,784&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;152&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,889&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;512,047&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,757&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(113&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,686&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,316,219&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;415&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,238&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,311,396&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;243,151&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,270&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(692&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;243,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;110,138&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;547&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;110,664&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;294,873&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,239&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(480&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;295,632&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,466&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,469&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;651,628&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,063&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,197&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;653,494&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,967,847&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,478&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,435&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,964,890&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;236&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,832&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,301&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Privately held equity securities included in deposits and other assets (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,115&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,001&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,125&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42,991&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;35,012&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,237&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,957&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49,292&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,002,859&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,715&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(17,392&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,014,182&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Includes investments classified as cash equivalents in our consolidated
            balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our publicly traded equity securities are included in other current
            assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2024, we recorded a $1.0 million net &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;unrealized loss in our consolidated statement of
              operations related to changes in the fair value of our investments in publicly traded companies.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at&lt;/span&gt; cost minus impairments, plus or minus changes resulting from observable price changes in
            orderly transactions for the identical or similar investment of the same issuer, which are Level 3 inputs. In the year ended December 31, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we recorded a $&lt;/span&gt;2.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million net unrealized loss in our consolidated statements of operations related to observable price changes of our investments in privately held companies.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following is a summary of our investments we considered to be temporarily impaired at&#160;&lt;/span&gt;December 31, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;(in thousands, except for number of investments):&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Less than 12 Months of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;More than 12 Months of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Temporary&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Investments&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;274&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;488,949&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,463&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,713&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(52&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;516,662&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,515&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;67,854&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(328&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;67,854&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(328&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;38&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;252,926&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(503&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,173&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(93&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;277,099&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(596&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%;"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;643&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;129&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;772&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;346&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;811,068&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,296&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52,015&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(145&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;863,083&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,441&lt;/div&gt;
        &lt;/td&gt;

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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;6. Fair Value Measurements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following tables present the major security types we held at December 31, 2024 and 2023&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;that we regularly measure and carry at fair value&lt;/span&gt;. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective
    securities&#x2019; fair value (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;180,445&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;180,445&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,032,066&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,032,066&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;208,998&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;208,998&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;806,724&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;806,724&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,524&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,524&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (3)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,241,716&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;992,432&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,249,284&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;185,424&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;185,424&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (4)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;801,228&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;801,228&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;334,828&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;334,828&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;807,679&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;807,679&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,155&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,155&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (3)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,301&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,301&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,156,615&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;999,404&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,157,211&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in cash and cash equivalents in our consolidated balance
            sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in short-term investments in our consolidated balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in other current assets in our consolidated balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$33.0 million was included in cash and cash equivalents, with the difference included in short-term investments in our consolidated balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Convertible Notes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our 1.75% Notes and 0% Notes had a fair value of $569.3 million and $612.8 million at December 31, 2024,
    respectively. Our 1.75% Notes, 0%
    Notes and 0.125% Notes had a fair value of $661.1
    million, $667.8 million and $42.4
    million at December 31, 2023, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are
    Level 2 measurements because the notes do not trade regularly.&lt;/div&gt;
</us-gaap:FairValueDisclosuresTextBlock>
    <us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock
      contextRef="c20240101to20241231"
      id="Text_161f38ed596b48a19876a8584a322dc2">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following tables present the major security types we held at December 31, 2024 and 2023&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;that we regularly measure and carry at fair value&lt;/span&gt;. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective
    securities&#x2019; fair value (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;180,445&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;180,445&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,032,066&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,032,066&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;208,998&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;208,998&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;806,724&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;806,724&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,524&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,524&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (3)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,241,716&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;992,432&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,249,284&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;185,424&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;185,424&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (4)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;801,228&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;801,228&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;334,828&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;334,828&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;807,679&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;807,679&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,155&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,155&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (3)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,301&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,301&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,156,615&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;999,404&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,157,211&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in cash and cash equivalents in our consolidated balance
            sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in short-term investments in our consolidated balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in other current assets in our consolidated balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;7. Long-Term Obligations and Commitments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The carrying value of our long-term obligations was as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

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    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;1.75&lt;/span&gt;%
            convertible senior notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;565,026&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;562,285&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;0&lt;/span&gt;%
            convertible senior notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;628,535&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;625,380&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Liability related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;542,212&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;513,736&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;170,869&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;178,969&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Mortgage debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,714&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,859&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other obligations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,425&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,714&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,958,781&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,922,943&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: current portion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,279&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(8,831&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total Long-Term Obligations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,949,502&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,914,112&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2023, our 0.125%
    Notes was classified as a current liability because they matured in December 2024.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Convertible Debt and Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;1.75 Percent
    Convertible Senior Notes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2023, we completed a $575.0
    million offering of our 0.125% Notes and used $488.2
    million of the net proceeds from the issuance of the 1.75% Notes to repurchase $504.4 million in principal of our 0.125% Notes. In December 2024, we
    used $44.5 million of the net proceeds to settle the remaining principal balance of our 0.125% Notes upon maturity.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2024, we had the
    following 1.75% Notes outstanding (in millions, except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1.75% Notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;575.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_6bfb094eab7041389566a848570cbbe5"&gt;June 2028&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.75&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.73&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;0 Percent
    Convertible Senior Notes and Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2021, we completed a $632.5
    million offering of our 0% Notes. We used $319.0
    million of the net proceeds from the issuance of our 0% Notes to pay the remaining $309.9 million principal balance of our 1% convertible senior notes, or 1% Notes, in 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2024, we had the
    following 0% Notes outstanding (in millions, except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0% Notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;632.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_77100aa329424b42b6f03dc4fa1e2472"&gt;April 2026&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.84&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76.39&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with the 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and
    selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% Notes by increasing the effective conversion
    price on our 0% Notes. We increased our effective conversion price to $76.39 with the same number of underlying shares as our 0% Notes. The
    call spread cost us $46.9 million, of which $136.7
    million was for the note hedge purchase, offset by $89.8 million we received for selling the warrants. Similar to our 0% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0% Notes. The note hedges will expire upon maturity of the 0%
    Notes, or &lt;span style="-sec-ix-hidden:Fact_c2c8af8268614a7d9201a587fc5822f5"&gt;April 2026&lt;/span&gt;. The note hedges and warrants are separate transactions and are not part of the terms of our 0% Notes. The holders of the 0% Notes do not
    have any rights with respect to the note hedges and warrants.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies&lt;/span&gt;, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;0.125 Percent
    Convertible Senior Notes and Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of
    our 1% Notes to exchange $375.6
    million of our 1% Notes for $439.3
    million of our 0.125% Notes, and to issue $109.5
    million of our 0.125% Notes.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As discussed above, in 2023, we repurchased $504.4
    million of our 0.125% Notes. As a result of the repurchase, we recognized a $13.4 million gain on the early retirement of debt, which we recorded as other income in our consolidated statement of operations for the year ended December 31, 2023. The gain on the early retirement of our debt is the difference between the amounts paid to repurchase our 0.125% Notes and the net carrying balance of the liability at the time that we completed the repurchases. We paid the remaining principal balance of our 0.125% Notes with $44.5 million of cash at
    maturity in December 2024.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In conjunction with the issuance of our &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes in 2019, we entered into a call spread transaction, which was
      comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our &lt;/span&gt;0.125%
    Notes by increasing the effective conversion price on our 0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We increased our effective conversion price from $&lt;/span&gt;83.28&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to $&lt;/span&gt;123.38&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; with the same number of underlying
      shares as our &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes. The call spread cost us $&lt;/span&gt;52.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, of which $&lt;/span&gt;108.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million was for the note hedge purchase, offset by $&lt;/span&gt;56.1&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million we received for selling the warrants. Similar to our &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, our note hedges were subject to adjustment. Additionally, our
      note hedges were exercisable upon conversion of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The note hedges expired upon maturity of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in &lt;/span&gt;&lt;span style="-sec-ix-hidden:Fact_b2783015cbc64323aab97584a4bd55af"&gt;December 2024&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The warrants will expire in
      March 2025. The note hedges and warrants were separate transactions and were not part of the terms of our &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The holders of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; did not have any rights with respect to the note hedges and warrants.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies&lt;/span&gt;, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Other Terms of Convertible Senior Notes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The 1.75% and 0% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash,
    shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of
    certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to 100 percent of the principal
    amount of the notes to be purchased, plus any accrued and unpaid interest. The 0.125% Notes were subject to similar terms.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our total interest expense for our outstanding senior convertible notes for the years ended December 31, 2024, 2023 and 2022 included $6.1 million, $5.9 million and $5.3 million, respectively, of
    non-cash interest expense related to the amortization of debt issuance costs for our convertible notes.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Financing Arrangements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Operating Facilities&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2017, we purchased the building that houses our primary R&amp;amp;D facility for $79.4 million and our manufacturing facility for $14.0 million. We
    financed the purchase of these two facilities with mortgage debt of $60.4 million in total. Our primary R&amp;amp;D facility mortgage had an interest rate of 3.88
    percent. Our manufacturing facility mortgage has an interest rate of 4.20 percent. During the first five years of both mortgages, we were only required to make interest payments. We began making principal payments in 2022. Our manufacturing facility mortgage matures in August
    2027. We repaid our primary R&amp;amp;D facility mortgage in 2022 in conjunction with a sale and leaseback transaction.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2022, we concurrently entered into two
    purchase and sale agreements with a real estate investor. In the same period, we closed the first transaction in which we sold the facilities at our headquarters in Carlsbad, California, which includes our primary R&amp;amp;D facility, for a purchase price
    of $263.4 million. As a result, we de-recognized the related land and improvements, building and building improvements, which resulted in a net
    gain of $150.1 million that we reported in other income in our consolidated statements of operations. We used a portion of the sale proceeds to
    extinguish our outstanding mortgage debt on our primary R&amp;amp;D facility of $51.3 million. In connection with this transaction, we leased back
    our headquarters facilities for an initial lease term of 15 years with options to extend the lease for two additional terms of five years each.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In August 2023, we closed the second transaction and transferred legal ownership of two lots of undeveloped land adjacent to our headquarters to the real estate investor for a purchase price of $33 million. In connection with this transaction, we entered into a build-to-suit lease agreement with the same real estate investor to lease a new R&amp;amp;D facility. The lessor will
    develop and construct a new building composed of R&amp;amp;D and office space. We will design and construct tenant improvements to customize the facility&#x2019;s interior space. We will lease the facility for an initial term of 15 years with options to extend the lease for two
    additional terms of five years each. The lease will commence once the structure of this new facility is completed.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Since the building is under construction and unavailable to lease, we are unable to complete the sale-leaseback evaluation under ASC 842,
    &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Leases&lt;/span&gt;. As a result, the land remains in our consolidated balance sheets and we accounted for the proceeds as a financial liability. We will
    reassess the transaction under the sale-leaseback accounting guidance when the facilities are available for lease commencement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Debt Maturity Schedules&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2024 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2025&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,657&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2026&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;643,157&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2027&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2028&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;580,091&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2029&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Thereafter&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;360&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total debt and mortgage maturities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,253,062&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Current portion included in other current liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(165&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Fixed and determinable interest&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(36,511&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13,981&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,202,405&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Royalty Revenue Monetization&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our agreements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $500 million and we are eligible to receive up to $625 million in additional milestone payments. Under the terms of
    the agreement, Royalty Pharma will receive 25 percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to 45 percent of royalty payments in 2028, on up to $1.5
    billion in annual sales. In addition, Royalty Pharma will receive 25 percent of any future royalty payments on pelacarsen. Royalty Pharma&#x2019;s
    royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $475 million or $550 million, depending on the timing and occurrence of FDA approval of pelacarsen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recorded the upfront payment of $500
    million as a liability related to the sale of future royalties, net of transaction costs of $10.4 million, which we are amortizing over the
    estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty
    Pharma as a reduction of the liability.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We determine the effective interest rate used to record
      interest expense under this agreement based on an estimate of future royalty payments to Royalty Pharma. As of &lt;/span&gt;December 31, 2024 and
    2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the estimated effective interest rate under the agreement
      was &lt;/span&gt;13.5 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following is a summary of our liability related to
      sale of future royalties for the year ended &lt;/span&gt;December 31, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; (in thousands):&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Proceeds from sale of future royalties in January 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;500,000&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Issuance costs related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,434&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Royalty payments to Royalty Pharma&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44,628&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;68,238&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amortization of issuance costs related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;560&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net liability related to sale of future royalties as of December 31, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;513,736&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Royalty payments to Royalty Pharma&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44,981&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,846&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amortization of issuance costs related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;611&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net liability related to sale of future royalties as of December 31, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;542,212&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty
    payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the commercial sales of SPINRAZA, the regulatory approval and commercial sales of
    pelacarsen, competing products or other significant events.&lt;/div&gt;
</us-gaap:DebtDisclosureTextBlock>
    <us-gaap:ScheduleOfDebtInstrumentsTextBlock
      contextRef="c20240101to20241231"
      id="Text_a4959bdb175f4cf6a490ada2282e4021">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The carrying value of our long-term obligations was as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;1.75&lt;/span&gt;%
            convertible senior notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;565,026&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;562,285&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;0&lt;/span&gt;%
            convertible senior notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;628,535&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;625,380&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Liability related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;542,212&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;513,736&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;170,869&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;178,969&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Mortgage debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,714&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,859&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other obligations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,425&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,714&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,958,781&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,922,943&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: current portion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,279&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(8,831&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total Long-Term Obligations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,949,502&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,914,112&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfDebtInstrumentsTextBlock>
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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      unitRef="U001">562285000</us-gaap:ConvertibleDebt>
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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      decimals="-3"
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      unitRef="U001">628535000</us-gaap:ConvertibleDebt>
    <us-gaap:ConvertibleDebt
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      decimals="-3"
      id="Fact_65be5fa6a2434040beb0d9ae2a2ca4aa"
      unitRef="U001">625380000</us-gaap:ConvertibleDebt>
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      contextRef="c20241231"
      decimals="-3"
      id="Fact_0d3477713a1c4a8a88765ea8505721f4"
      unitRef="U001">542212000</ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet>
    <ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet
      contextRef="c20231231"
      decimals="-3"
      id="Fact_0bd1dad24d2643279f4173819bd5adf1"
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    <us-gaap:LoansPayableToBank
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      decimals="-3"
      id="Fact_7526ddee5b884532b24be01e4d495612"
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    <us-gaap:LoansPayableToBank
      contextRef="c20231231"
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      id="Fact_1a31cb06bce14608b6b4bc53c537a2e8"
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    <ions:LongTermObligationsCurrent
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    <us-gaap:ProceedsFromConvertibleDebt
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      id="Fact_039a4d1b01a34bf1820a24371b146141"
      unitRef="U001">504400000</us-gaap:RepaymentsOfConvertibleDebt>
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      decimals="5"
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2024, we had the
    following 1.75% Notes outstanding (in millions, except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1.75% Notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;575.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_6bfb094eab7041389566a848570cbbe5"&gt;June 2028&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.75&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.73&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2024, we had the
    following 0% Notes outstanding (in millions, except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0% Notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;632.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_77100aa329424b42b6f03dc4fa1e2472"&gt;April 2026&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.84&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76.39&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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    <srt:ContractualObligationFiscalYearMaturityScheduleTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_16539426e6924191b5cc465550dba8af">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2024 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2025&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,657&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2026&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;643,157&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2027&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2028&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;580,091&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2029&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Thereafter&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;360&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total debt and mortgage maturities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,253,062&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Current portion included in other current liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(165&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Fixed and determinable interest&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(36,511&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13,981&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,202,405&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</srt:ContractualObligationFiscalYearMaturityScheduleTableTextBlock>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths
      contextRef="c20241231"
      decimals="-3"
      id="Fact_d2eb54062a6d4f188ef1dbae3b8653d3"
      unitRef="U001">10657000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo
      contextRef="c20241231"
      decimals="-3"
      id="Fact_c42e928b65cd45aa923675e567769ac7"
      unitRef="U001">643157000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree
      contextRef="c20241231"
      decimals="-3"
      id="Fact_6b7eb3455bef4825bec5934f0ca8a9f2"
      unitRef="U001">18737000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour
      contextRef="c20241231"
      decimals="-3"
      id="Fact_5163088d8dfb4bd8afb6a945c3e15b83"
      unitRef="U001">580091000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive
      contextRef="c20241231"
      decimals="-3"
      id="Fact_04194527fb664e52a3ac79595e34b654"
      unitRef="U001">60000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive
      contextRef="c20241231"
      decimals="-3"
      id="Fact_74f3f2a83bb64af5b0b4b21df7d35ef0"
      unitRef="U001">360000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive>
    <us-gaap:LongTermDebt
      contextRef="c20241231"
      decimals="-3"
      id="Fact_41f58f8c96774a38af7b7c1cc41eabb9"
      unitRef="U001">1253062000</us-gaap:LongTermDebt>
    <us-gaap:LongTermDebtCurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_bc879ac3c37f49de90a976632193e86e"
      unitRef="U001">165000</us-gaap:LongTermDebtCurrent>
    <us-gaap:InterestPayableCurrentAndNoncurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_ef9db53e88e14db9b13d2afa08b9cc23"
      unitRef="U001">36511000</us-gaap:InterestPayableCurrentAndNoncurrent>
    <us-gaap:DeferredFinanceCostsNet
      contextRef="c20241231"
      decimals="-3"
      id="Fact_97e59891cc4a4a90baf9d56b32982707"
      unitRef="U001">13981000</us-gaap:DeferredFinanceCostsNet>
    <us-gaap:LongTermDebtNoncurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_2e8033307b594b4f9b2e30ee6ba95bc3"
      unitRef="U001">1202405000</us-gaap:LongTermDebtNoncurrent>
    <us-gaap:LesseeOperatingLeasesTextBlock
      contextRef="c20240101to20241231"
      id="Text_816a383efe384026825a397c06709b4a">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Operating Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Carlsbad Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing
    facility. We lease this space under a non-cancelable operating lease. In 2020, we exercised our option to extend our lease, extending our lease term from June 2021 to August 2026. We have one remaining option to extend the lease for an additional five-year
    period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also lease an additional office space and warehouse space in Carlsbad. We lease these spaces under non-cancelable operating leases. In
    2022, we exercised our option to extend the office space lease, extending our term from January 2023 to May 2027. We have no remaining options
    to extend this lease. Our warehouse space lease in Carlsbad has an initial term ending in 2028 with no options to extend the lease.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As discussed above in the section titled, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Financing Arrangements&lt;/span&gt;, we lease our headquarters, which includes our primary R&amp;amp;D facility, as part of a sale and leaseback transaction that closed in 2022. The initial lease term for our headquarters facilities is 15 years with options to extend the lease for two
    additional terms of five years each. We determined at lease inception that it was not reasonably certain that we would exercise any of the
    options to extend the lease. We expect our lease payments over the initial term to total approximately $280 million. In connection with the
    transfer of legal ownership of the two lots of undeveloped land to the real estate investor, we entered into a build-to-suit lease agreement
    with the same real estate investor who will build a new R&amp;amp;D facility for us on those lots. The lease will commence once the structure of this new facility is completed.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Oceanside Lease&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility to be constructed by
    the lessor in Oceanside, California. We capitalized costs that we incurred related to the design and development of tenant improvements as construction-in-progress in our consolidated balance sheets. In 2023, we reached a mutual agreement with the
    lessor to terminate the lease agreement. As a result, we recorded a charge of $20 million, primarily associated with the impairment of
    construction-in-progress assets, within &lt;span style="-sec-ix-hidden:Fact_ebdf1ed5cf6845079198439e7c520f42"&gt;SG&amp;amp;A expense&lt;/span&gt; in our consolidated statements of operations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Boston Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We entered into an operating lease agreement for office space located in Boston, Massachusetts which commenced in August 2018. We are
    leasing this space under a non-cancelable operating lease with an initial term ending after 123 months and an option to extend the lease for an
    additional five-year term. Under the lease agreement, we received a three-month free rent period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commencement date was in
    January 2022 when the office space was ready for our tenant&#x2019;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending 83 months following the sublease commencement date with no option to extend the sublease. Under the sublease
    agreement we provided a seven-month free rent period, which commenced in January 2022. We will receive lease payments over the sublease term
    totaling $9.6 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We entered into an operating lease agreement for another office space located in Boston, Massachusetts which commenced in 2021. We are
    leasing this space under a non-cancelable operating lease with an initial term ending 91 months following the lease commencement date and an
    option to extend the lease for &lt;span style="-sec-ix-hidden:Fact_ddceec580074417fbe536c7c2d5d252c"&gt;an&lt;/span&gt; additional five-year
    term. Under the lease agreement, we received a seven-month free rent period, which commenced in November 2021. Our lease payments over the
    initial term total $6.8 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases, we did not include
    the extension options for these leases in the original lease term because it was not reasonably certain we would exercise those extension options.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts related to our operating leases were as follows (dollar amounts in millions):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At December 31, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Right-of-use operating lease assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;161.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;170.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average remaining lease term&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12.1 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average discount rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024,
    2023, and 2022 we paid $20.5 million, $20.1 million and $4.0 million of lease payments, which were included in operating activities in our consolidated statements of cash flows.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2024,
    the future payments for our operating lease liabilities are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Operating&lt;/span&gt; &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Leases&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Year ending December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2025&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,870&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2026&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,032&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2027&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,054&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2028&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,973&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2029&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,687&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Thereafter&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;157,622&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total minimum lease payments&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;260,238&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Imputed interest&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(89,369&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Current portion (included in &lt;span style="-sec-ix-hidden:Fact_9874929ec96442469df0f0fc39baed32"&gt;other current liabilities&lt;/span&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,064&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total long-term lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;161,805&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Rent expense was $23.2 million,
    $23.1 million and $8.3 million for the
    years ended December 31, 2024, 2023
    and 2022, respectively. &lt;/div&gt;
</us-gaap:LesseeOperatingLeasesTextBlock>
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    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember"
      decimals="-6"
      id="Fact_a1b244754eec475a945bcce4913ec530"
      unitRef="U001">280000000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue>
    <ions:NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor
      contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember"
      decimals="INF"
      id="Fact_17aadca36cd14bb7b824374f744e4abc"
      unitRef="U018">2</ions:NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor>
    <us-gaap:ImpairmentOfLongLivedAssetsHeldForUse
      contextRef="c20230101to20231231_PropertyPlantAndEquipmentByTypeAxis_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember"
      decimals="-6"
      id="Fact_171f16cc89494c4ea4ec3ca4d9a325d8"
      unitRef="U001">20000000</us-gaap:ImpairmentOfLongLivedAssetsHeldForUse>
    <us-gaap:LesseeOperatingLeaseTermOfContract
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember"
      id="Fact_1cf767bfa2604645b03665b44c8069bb">P123M</us-gaap:LesseeOperatingLeaseTermOfContract>
    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember"
      id="Fact_c9d11c93abf3409aab88ca3e2efcb6a1">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <ions:LesseeOperatingLeasePeriodOfFreeRent
      contextRef="c20240101to20241231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember"
      id="Fact_ba6fa8c8bcc140258a36c6828c2ab217">P3M</ions:LesseeOperatingLeasePeriodOfFreeRent>
    <us-gaap:LessorOperatingLeaseTermOfContract
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember"
      id="Fact_f3673b6f6d8a469cb3fc9b19fe6c9445">P83M</us-gaap:LessorOperatingLeaseTermOfContract>
    <ions:LessorOperatingLeaseNumberOfOptionsToExtendLease
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember"
      decimals="INF"
      id="Fact_8c1775b36c92469e9d8ba3d06078efc9"
      unitRef="U019">0</ions:LessorOperatingLeaseNumberOfOptionsToExtendLease>
    <ions:LessorOperatingLeasePeriodOfFreeRent
      contextRef="c20240101to20241231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember"
      id="Fact_bdb3d42dbeaf484494c12e827a769a24">P7M</ions:LessorOperatingLeasePeriodOfFreeRent>
    <us-gaap:LessorOperatingLeasePaymentsToBeReceived
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember"
      decimals="-5"
      id="Fact_7c8de04d910848adb798d3e411c0825d"
      unitRef="U001">9600000</us-gaap:LessorOperatingLeasePaymentsToBeReceived>
    <us-gaap:LesseeOperatingLeaseTermOfContract
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      id="Fact_f252e6bc1ca849dfb22869bd4a71369a">P91M</us-gaap:LesseeOperatingLeaseTermOfContract>
    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      id="Fact_093b7e88a1474547a8fe7129936aa7cd">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <ions:LesseeOperatingLeasePeriodOfFreeRent
      contextRef="c20240101to20241231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      id="Fact_99931a7181e04c71bbd9180a5f64f952">P7M</ions:LesseeOperatingLeasePeriodOfFreeRent>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue
      contextRef="c20241231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      decimals="-5"
      id="Fact_c350c485d2194852998ea1b496903ff5"
      unitRef="U001">6800000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue>
    <ions:LesseeOperatingLeaseInformationTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_e4fd6084d7e2468e95eebcfebd153735">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts related to our operating leases were as follows (dollar amounts in millions):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At December 31, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Right-of-use operating lease assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;161.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;170.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average remaining lease term&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12.1 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average discount rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</ions:LesseeOperatingLeaseInformationTableTextBlock>
    <us-gaap:OperatingLeaseRightOfUseAsset
      contextRef="c20241231"
      decimals="-5"
      id="Fact_42b72db309654cf1bdbfe546a3a2176d"
      unitRef="U001">161900000</us-gaap:OperatingLeaseRightOfUseAsset>
    <us-gaap:OperatingLeaseLiability
      contextRef="c20241231"
      decimals="-5"
      id="Fact_44caa1523d334df48c7b2561738097e4"
      unitRef="U001">170900000</us-gaap:OperatingLeaseLiability>
    <us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1
      contextRef="c20241231"
      id="Fact_ccfd1bbd8568445fb43b6a1d85973cc7">P12Y1M6D</us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1>
    <us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent
      contextRef="c20241231"
      decimals="3"
      id="Fact_0f6726aa9c174130a3010b4dad4799ef"
      unitRef="U003">0.069</us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent>
    <us-gaap:OperatingLeasePayments
      contextRef="c20240101to20241231"
      decimals="-5"
      id="Fact_826cead5743b4e90a9d8b807e97fe422"
      unitRef="U001">20500000</us-gaap:OperatingLeasePayments>
    <us-gaap:OperatingLeasePayments
      contextRef="c20230101to20231231"
      decimals="-5"
      id="Fact_297fcce7f2e44b348fe63e7be360cf7c"
      unitRef="U001">20100000</us-gaap:OperatingLeasePayments>
    <us-gaap:OperatingLeasePayments
      contextRef="c20220101to20221231"
      decimals="-5"
      id="Fact_50e928616e964a8c94f28d1e4409995c"
      unitRef="U001">4000000</us-gaap:OperatingLeasePayments>
    <us-gaap:LesseeOperatingLeaseLiabilityMaturityTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_4ac550fe12b346a487d1639e48d94f8d">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2024,
    the future payments for our operating lease liabilities are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Operating&lt;/span&gt; &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Leases&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Year ending December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2025&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,870&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2026&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,032&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2027&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,054&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2028&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,973&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2029&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,687&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Thereafter&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;157,622&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total minimum lease payments&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;260,238&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Imputed interest&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(89,369&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Current portion (included in &lt;span style="-sec-ix-hidden:Fact_9874929ec96442469df0f0fc39baed32"&gt;other current liabilities&lt;/span&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,064&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total long-term lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;161,805&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:LesseeOperatingLeaseLiabilityMaturityTableTextBlock>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths
      contextRef="c20241231"
      decimals="-3"
      id="Fact_9240bc8118ea402f85a2119c7486d19d"
      unitRef="U001">20870000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo
      contextRef="c20241231"
      decimals="-3"
      id="Fact_4609f99ef9604c9aae3baed51a3c3fed"
      unitRef="U001">21032000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearThree
      contextRef="c20241231"
      decimals="-3"
      id="Fact_d11239309f5945a3891ef526d1491daa"
      unitRef="U001">21054000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearThree>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFour
      contextRef="c20241231"
      decimals="-3"
      id="Fact_43a6c7550e004272b7f9ca99a8ba22d8"
      unitRef="U001">20973000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFour>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFive
      contextRef="c20241231"
      decimals="-3"
      id="Fact_74899d789ebf4c2ebccd545b74c63e21"
      unitRef="U001">18687000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFive>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive
      contextRef="c20241231"
      decimals="-3"
      id="Fact_3931369a624044a9b1905cb93b92544f"
      unitRef="U001">157622000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue
      contextRef="c20241231"
      decimals="-3"
      id="Fact_3603a725690b46dda9be3db4e21043c4"
      unitRef="U001">260238000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue>
    <us-gaap:LesseeOperatingLeaseLiabilityUndiscountedExcessAmount
      contextRef="c20241231"
      decimals="-3"
      id="Fact_6d8e7a3e7ccb4ac9a37ea341d9cadf8c"
      unitRef="U001">89369000</us-gaap:LesseeOperatingLeaseLiabilityUndiscountedExcessAmount>
    <us-gaap:OperatingLeaseLiabilityCurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_599739bca7c14726b6810c3c3a59fcff"
      unitRef="U001">9064000</us-gaap:OperatingLeaseLiabilityCurrent>
    <us-gaap:OperatingLeaseLiabilityNoncurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_5bc4a22d2bca49aca884201dc1170194"
      unitRef="U001">161805000</us-gaap:OperatingLeaseLiabilityNoncurrent>
    <us-gaap:OperatingLeaseExpense
      contextRef="c20240101to20241231"
      decimals="-5"
      id="Fact_b625c294a3bd434f8c74620b51e1ea20"
      unitRef="U001">23200000</us-gaap:OperatingLeaseExpense>
    <us-gaap:OperatingLeaseExpense
      contextRef="c20230101to20231231"
      decimals="-5"
      id="Fact_37e7125f4da2437a81d1b7f1853e4554"
      unitRef="U001">23100000</us-gaap:OperatingLeaseExpense>
    <us-gaap:OperatingLeaseExpense
      contextRef="c20220101to20221231"
      decimals="-5"
      id="Fact_a6f37ce5e1654e67b6bfb04f2bfaa94b"
      unitRef="U001">8300000</us-gaap:OperatingLeaseExpense>
    <ions:UpfrontRoyaltyPaymentReceived
      contextRef="c20230101to20230131"
      decimals="-6"
      id="Fact_c8ba625af5db4c629715e10efedcdff1"
      unitRef="U001">500000000</ions:UpfrontRoyaltyPaymentReceived>
    <ions:MaximumAmountOfPaymentsReceivableForAdditionalMilestones
      contextRef="c20230131"
      decimals="-6"
      id="Fact_d5508d985dec4c9299c67fd453890fd5"
      unitRef="U001">625000000</ions:MaximumAmountOfPaymentsReceivableForAdditionalMilestones>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember"
      decimals="2"
      id="Fact_04d45df1075f4c7282dba5c75f87090a"
      unitRef="U003">0.25</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember"
      decimals="2"
      id="Fact_7db57813067c495a9024650b8968a999"
      unitRef="U003">0.45</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid
      contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember"
      decimals="-8"
      id="Fact_9f09740d482b4450bde402e99f9264a9"
      unitRef="U001">1500000000</ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20230131_ProductOrServiceAxis_PelacarsenMember"
      decimals="2"
      id="Fact_4f14fcd874cc407499d3f48e153e6244"
      unitRef="U003">0.25</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack
      contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember"
      decimals="-6"
      id="Fact_2203af9e770d4ee987086d61868bd2ee"
      unitRef="U001">475000000</ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack>
    <ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack
      contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember"
      decimals="-6"
      id="Fact_dcfdc1338630420c9019168b9412101d"
      unitRef="U001">550000000</ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack>
    <ions:UpfrontRoyaltyPaymentReceived
      contextRef="c20230101to20230131"
      decimals="-6"
      id="Fact_f0e73629c96a44169a5a0e9d8a1d4b9a"
      unitRef="U001">500000000</ions:UpfrontRoyaltyPaymentReceived>
    <ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties
      contextRef="c20240101to20241231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-5"
      id="Fact_1391ba32fa9a456194c1aa68413d1b61"
      unitRef="U001">10400000</ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="3"
      id="Fact_ec437319099f426c8aa516986b8454b2"
      unitRef="U003">0.135</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20241231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="3"
      id="Fact_d7d548cc748640208f68b9bf1f4a17e2"
      unitRef="U003">0.135</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:OtherNoncurrentLiabilitiesTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_21736a72e1aa4319a1ee1097952860ac">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following is a summary of our liability related to
      sale of future royalties for the year ended &lt;/span&gt;December 31, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; (in thousands):&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Proceeds from sale of future royalties in January 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;500,000&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Issuance costs related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,434&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Royalty payments to Royalty Pharma&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44,628&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;68,238&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amortization of issuance costs related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;560&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net liability related to sale of future royalties as of December 31, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;513,736&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Royalty payments to Royalty Pharma&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44,981&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,846&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amortization of issuance costs related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;611&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net liability related to sale of future royalties as of December 31, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;542,212&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:OtherNoncurrentLiabilitiesTableTextBlock>
    <ions:ProceedsFromSaleOfFutureRoyalties
      contextRef="c20230101to20230131_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_b900ad354383483f9c34ba3b6c879d07"
      unitRef="U001">500000000</ions:ProceedsFromSaleOfFutureRoyalties>
    <ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_06f0683a1ee2471e904766301687d1bf"
      unitRef="U001">10434000</ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties>
    <ions:RoyaltyPayments
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_67ccd0c0a7a24a5f910faba6121087a7"
      unitRef="U001">44628000</ions:RoyaltyPayments>
    <ions:InterestExpenseRelatedToSaleOfFutureRoyalties
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    <us-gaap:StockholdersEquityNoteDisclosureTextBlock
      contextRef="c20240101to20241231"
      id="Text_334061329e6345ae91c6341ea13083ef">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;8. Stockholders&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt; Equity&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Preferred Stock&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are authorized to issue up to 15
    million shares of &#x201c;blank check&#x201d; Preferred Stock. As of December 31, 2024, there were no shares of Preferred Stock outstanding. We have designated Series C Junior Participating Preferred Stock but have no issued or outstanding shares as of December 31, 2024.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Common Stock&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2024 and 2023, we had 300 million shares of common
    stock authorized, of which 157.9 million and 144.3 million were issued and outstanding, respectively. As of December 31, 2024, total common shares
    reserved for future issuance were 48.0 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2024,
    2023 and 2022, we issued 2.1 million, 2.3 million and 1.2 million shares of common stock, respectively, for stock option exercises, vesting of restricted stock units, and ESPP purchases. We received net
    proceeds from these transactions of $33.6 million, $49.4
    million and $6.4 million in 2024, 2023 and 2022, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In September 2024, we completed the sale of 11.5
    million shares of our common stock through a public offering at a price of $43.50 per share. We received net proceeds of $489.1 million from the sale of these shares net of underwriting discounts and commissions and other offering expenses of $11.2 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock Plans&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;1989 Stock Option Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 1989, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that, as amended, provides for
    the issuance of non-qualified and incentive stock options for the purchase of up to 20.0 million shares of common stock to our employees,
    directors, and consultants. The plan expired in January 2024. The 1989 Stock Option Plan, or 1989 Plan, did not allow us to grant stock bonuses or restricted stock awards and prohibited us from repricing any options outstanding under the plan unless
    our stockholders approved the repricing. Options vested over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant
    and the balance vested ratably, on a monthly basis, thereafter and had a term of seven years. At December 31, 2024, no options were outstanding and no shares were available for future grant under the 1989 Plan.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2011 Equity Incentive Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the issuance of
    stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to our employees, directors, and consultants. In June 2015, May 2017 and June 2019, after receiving approval from our
    stockholders, we amended our 2011 Equity Incentive Plan, or&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; 2011 Plan,&lt;/span&gt; to increase the total number of shares reserved for issuance. We increased the shares available
    under our 2011 Equity Incentive Plan from 5.5 million to 11.0 million in June 2015, from 11.0 million to 16.0 million in May 2017 and from 16.0 million to 23.0 million in June 2019. In June 2021, after receiving approval from our stockholders, we amended our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2011 Plan. The amendment increased the total number of shares of common stock authorized for issuance under the 2011 Plan from &lt;/span&gt;23.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to &lt;/span&gt;29.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and added a fungible share counting ratio whereby the share reserve will be reduced by &lt;/span&gt;1.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; shares for each share of common stock issued pursuant to a full value award (i.e., RSU or PRSU) and
      increased by &lt;/span&gt;1.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; shares for each share of common stock
      returning from a full value award. &lt;/span&gt;In June 2023, after receiving approval from our stockholders, we amended our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2011 Plan to increase the total number of shares of
      common stock authorized for issuance under the 2011 Plan from &lt;/span&gt;29.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to &lt;/span&gt;35.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. &lt;/span&gt;In June 2024,
    after receiving approval from our stockholders, we amended our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2011 Plan to increase the total number of shares of common stock authorized for issuance under the 2011 Plan
      from &lt;/span&gt;35.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to &lt;/span&gt;38.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The plan expires in June 2031. The 2011 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock
    appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our
    stockholders approve such action. Currently we anticipate awarding only stock options, RSU and PRSU awards to our employees, directors and consultants. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. Options granted after December 31, 2021 have a term of ten years.
    We have granted restricted stock unit awards to our employees under the 2011 Plan which vest annually over a four-year period. At December 31, 2024, a total of 13.3 million
    options were outstanding, of which 9.0 million were exercisable, 3.9 million restricted stock unit awards were outstanding, and 7.3 million shares were available for future grant
    under the 2011 Plan.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under the 2011 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur. In addition, we implemented a change of control and severance benefit plan that provides for change of control and severance benefits to our executive officers, including our
    chief executive officer and chief financial officer, and vice presidents. If one of our executive officers or vice presidents is terminated or
    resigns for good reason during the period that begins three months before and ends twelve months following a change in control of the company, the impacted employee&#x2019;s stock options and RSUs vesting will accelerate for options and RSUs outstanding as of the
    termination date.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2020 Equity Incentive Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In connection with the Akcea Merger in 2020, we assumed the
      unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or
      2020 Plan. The 2020 Plan provided for the issuance of up to &lt;/span&gt;2.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million shares of our Common Stock to our employees, directors and consultants who were employees of Akcea prior to the Akcea Merger. In the second quarter of 2021, our Compensation Committee approved an amendment to the 2020 Plan. The
      amendment decreased the total number of shares of common stock authorized for issuance under the 2020 Plan from approximately &lt;/span&gt;2.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to &lt;/span&gt;1.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. We assumed the 2020 Plan in connection with Ionis&#x2019; reacquisition of all of the outstanding shares of Akcea Therapeutics, Inc. as part of the Akcea Merger.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The plan expires in December 2025. The 2020 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock
    appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our
    stockholders approve such action. Currently we anticipate awarding only stock options and RSU awards to our eligible employees, directors and consultants. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. Options granted after December 31, 2021 have a term of ten years.
    We have granted restricted stock unit awards to our employees under the 2020 Plan which vest annually over a four-year period. At December 31, 2024, a total of 0.5 million
    options were outstanding, of which 0.2 million were exercisable, 0.2 million restricted stock unit awards were outstanding, and 0.8 million shares were available for future grant
    under the 2020 Plan.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under the 2020 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Corporate Transactions and Change in Control under 2011 and 2020 Plans&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the event of certain significant corporate transactions, our Board of Directors has the discretion to take one or more of the following
    actions with respect to outstanding stock awards under the 2011 and 2020 Plans:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;arrange for assumption, continuation, or substitution of a stock award by a surviving or acquiring entity (or its parent company);&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;arrange for the assignment of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award to the surviving or
            acquiring corporation (or its parent company);&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;accelerate the vesting and exercisability of a stock award followed by the termination of the stock award;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;arrange for the lapse of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;cancel or arrange for the cancellation of a stock award, to the extent not vested or not exercised prior to the effective date of the corporate transaction, in exchange
            for cash consideration, if any, as the Board, in its sole discretion, may consider appropriate; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;arrange for the surrender of a stock award in exchange for a payment equal to the excess of (a) the value of the property the holder of the stock award would have
            received upon the exercise of the stock award, over (b) any exercise price payable by such holder in connection with such exercise.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2002 Non-Employee Directors&#x2019; Stock Option Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2001, our Board of Directors adopted, and the stockholders subsequently approved, an amendment and restatement of the 1992 Non-Employee
    Directors&#x2019; Stock Option Plan, which provides for the issuance of non-qualified stock options and restricted stock units to our non-employee directors. The name of the resulting plan is the 2002 Non-Employee Directors&#x2019; Stock Option Plan, or the 2002
    Plan. In 2015, after receiving approval from our stockholders, we amended our 2002 Plan to increase the total number of shares reserved for issuance from 1.2
    million to 2.0 million. In 2020, after receiving approval from our stockholders, we further amended our 2002 Plan. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The amendments included:&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;An increase to the total number of shares reserved for issuance under the plan from &lt;/span&gt;2.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to &lt;/span&gt;2.8&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million shares;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;A reduction to the amount of the automatic awards under the plan;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;A revision to the vesting schedule of new awards granted; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"&gt;&lt;/td&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;An extension of the term of the plan.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Options under this plan expire 10 years
    from the date of grant. At December 31, 2024, a total of 0.9 million options were outstanding, of which 0.8 million were exercisable, 52,000 restricted stock unit awards were outstanding, and 0.4 million
    shares were available for future grant under the 2002 Plan.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Purchase Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2009, our Board of Directors adopted, and the stockholders subsequently approved, the amendment and restatement of the ESPP and we
    reserved an additional 150,000 shares of common stock for issuance thereunder. In each of the subsequent years until 2019, we reserved an
    additional 150,000 shares of common stock for the ESPP resulting in a total of 3.2 million shares authorized under the plan as of December 31, 2024.
    The ESPP permits full-time employees to purchase common stock through payroll deductions (which cannot exceed 10 percent of each employee&#x2019;s
    compensation) at the lower of 85 percent of fair market value at the beginning of the purchase period or the end of each purchase period. Under
    the amended and restated ESPP, employees must hold the stock they purchase for a minimum of six months from the date of purchase. During 2024, employees purchased and we issued to employees 0.1
    million shares under the ESPP at a weighted average price of $35.93 per share. At December 31, 2024, there were 0.3 million shares available for
    purchase under the ESPP.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock Option Activity&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the stock option activity under our stock plans for the year ended December 31, 2024 (in thousands, except per share and contractual life data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Exercise&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Price Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Remaining&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contractual Term&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Years)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Aggregate&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intrinsic&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Outstanding at December 31, 2023&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,091&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48.43&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49.77&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Exercised&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(399&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39.55&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited/expired&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,704&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.40&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Outstanding at December 31, 2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,717&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48.23&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.27&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,692&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Exercisable at December 31, 2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,089&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49.85&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3.66&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,460&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The weighted-average estimated fair values of options granted were $24.37, $19.72 and $18.66 for the years ended December 31, 2024, 2023 and 2022, respectively. The total
    intrinsic value of options exercised during the years ended December 31, 2024, 2023 and 2022 were $3.6 million, $6.0 million and $1.4 million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $15.8 million, $65.1 million and $3.6 million for the years ended December 31, 2024, 2023 and 2022, respectively. For the year
    ended December 31, 2024, the weighted-average fair value of options exercised was $48.59. As of December 31, 2024, total unrecognized compensation cost
    related to non-vested stock options was $43.7 million. We expect to recognize this cost over a weighted average period of 1.1 years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Restricted Stock Unit Activity&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the RSU activity for the year ended December 31, 2024 (in thousands, except per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Grant Date Fair&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2023&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,239&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43.40&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,005&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.92&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Vested&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,185&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46.88&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(228&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46.83&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,831&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46.06&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2024,
    2023 and 2022, the
    weighted-average grant date fair value of RSUs granted was $50.92, $40.51 and $36.14 per RSU, respectively. As of December 31, 2024, total unrecognized compensation cost related to RSUs was $72.6 million. We expect to recognize this cost over a weighted average period of 1.3 years. We will adjust the
    total unrecognized compensation cost for future changes in estimated forfeitures.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Performance Restricted Stock Unit Activity&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the PRSU activity for the year ended December 31, 2024 (in thousands, except per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Grant Date Fair&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2023&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;226&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56.04&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;179&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;78.41&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Vested&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(73&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.35&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;68.21&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;307&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;66.72&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2024,
    2023 and 2022, the
    weighted-average grant date fair value of PRSUs granted was $78.41, $57.43 and $42.28 per PRSU, respectively. As of December 31, 2024, total unrecognized compensation cost related to PRSUs was $10.4 million. We expect to recognize this cost over a weighted average period of 1.4 years. We will adjust the
    total unrecognized compensation cost for future changes in estimated forfeitures.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock-based Compensation Expense and Valuation Information&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes stock-based compensation expense for the years ended December 31, 2024, 2023 and 2022 (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cost of sales&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;767&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;499&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;533&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research, development and patent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;92,403&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,826&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;73,704&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;37,030&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,484&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,027&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation expense, net of amounts capitalized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,200&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105,809&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100,264&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Capitalized stock-based compensation expense&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;799&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total stock-based compensation expense&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,999&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105,809&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100,264&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation expense increased in 2024 compared to 2023 due to increased headcount and a higher stock price on the grant date
    of annual equity awards in 2024 compared to 2023. Refer to Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and Significant Accounting Policies&lt;/span&gt;, for further details on how we
    determine the fair value of stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2024,
    2023 and 2022, we used the
    following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.3 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.3 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.3 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Board of Director Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.5 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.7 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.4 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;ESPP:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;37.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;36.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Risk-Free Interest Rate.&lt;/span&gt; We base
    the risk-free interest rate assumption on observed interest rates appropriate for the term of our stock option plans or ESPP.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Dividend Yield.&lt;/span&gt; We base the
    dividend yield assumption on our history and expectation of dividend payouts. We have not paid dividends in the past and do not expect to in the future.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Volatility.&lt;/span&gt; We use an average of
    the historical stock price volatility of our stock for the Black-Scholes model. We computed the historical stock volatility based on the expected term of the awards.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Expected Life. &lt;/span&gt;The expected term
    of stock options we have granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options we have granted based on actual and projected exercise patterns. In 2021, our Compensation
    Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options granted under these plans from &lt;span style="-sec-ix-hidden:Fact_bd3d24dad695460d8e7018466f08295c"&gt;&lt;span style="-sec-ix-hidden:Fact_a0ee4419d26449d89aee22da843bd7ad"&gt;seven&lt;/span&gt;&lt;/span&gt; to ten years for stock options granted on January 1, 2022
    and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other
    means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the years ended December 31, 2024, 2023 and 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical
    information, we will transition to calculating our expected term based on our historical exercise patterns.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Forfeitures.&lt;/span&gt; We reduce stock-based
    compensation expense for estimated forfeitures. We estimate forfeitures at the time of grant and revise, if necessary, in subsequent periods if actual forfeitures differ from those estimates. We estimate forfeitures based on historical experience. &lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the stock option activity under our stock plans for the year ended December 31, 2024 (in thousands, except per share and contractual life data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Exercise&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Price Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Remaining&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contractual Term&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Years)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Aggregate&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intrinsic&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Outstanding at December 31, 2023&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,091&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48.43&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49.77&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Exercised&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(399&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39.55&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited/expired&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,704&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.40&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Outstanding at December 31, 2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,717&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48.23&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.27&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,692&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Exercisable at December 31, 2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,089&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49.85&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3.66&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,460&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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    <ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue
      contextRef="c20240101to20241231_AwardTypeAxis_StockOptionMember"
      decimals="2"
      id="Fact_2b17593a26f3421991429bedce8b1c41"
      unitRef="U004">48.59</ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions
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      decimals="-5"
      id="Fact_72c37b7b47114b45a9abf8d6722faa52"
      unitRef="U001">43700000</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions>
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    <us-gaap:ScheduleOfSharebasedCompensationRestrictedStockAndRestrictedStockUnitsActivityTableTextBlock
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the RSU activity for the year ended December 31, 2024 (in thousands, except per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Grant Date Fair&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2023&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,239&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43.40&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,005&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.92&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Vested&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,185&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46.88&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(228&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46.83&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,831&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46.06&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfSharebasedCompensationRestrictedStockAndRestrictedStockUnitsActivityTableTextBlock>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber
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      id="Fact_9b79ad26dfed4644a99778a07c2788e7"
      unitRef="U002">3239000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue
      contextRef="c20231231_AwardTypeAxis_RestrictedStockUnitsRSUMember"
      decimals="2"
      id="Fact_7b0c381469384de4a83c2d06c591c7e0"
      unitRef="U004">43.4</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod
      contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember"
      decimals="-3"
      id="Fact_1bdc071fcc1b43c49a958a8b0de0d593"
      unitRef="U002">2005000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue
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      decimals="2"
      id="Fact_029b251fe1ed4825bb24ef350c208693"
      unitRef="U004">50.92</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod
      contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember"
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      id="Fact_32f1bead9c704269b614ad1cd037ad04"
      unitRef="U002">1185000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue
      contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember"
      decimals="2"
      id="Fact_df38f96941f0458f9ca876b79bbed1b6"
      unitRef="U004">46.88</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod
      contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember"
      decimals="-3"
      id="Fact_22694e1383774415bf4c78c2ec3ee1f6"
      unitRef="U002">228000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue
      contextRef="c20240101to20241231_AwardTypeAxis_RestrictedStockUnitsRSUMember"
      decimals="2"
      id="Fact_d3684b8ecd434d79a0c627293baaf219"
      unitRef="U004">46.83</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue>
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      decimals="-3"
      id="Fact_28559434ff5b402683a66fe056752875"
      unitRef="U002">3831000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue
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      decimals="2"
      id="Fact_5d0497b5899240c48adeef1f11e34ed4"
      unitRef="U004">46.06</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue
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      decimals="2"
      id="Fact_6c1a06db93094900a762b6eb164c546f"
      unitRef="U004">50.92</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue
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      decimals="2"
      id="Fact_43f43b5a78cc4be1918b46bdde39a8d8"
      unitRef="U004">40.51</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue
      contextRef="c20220101to20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember"
      decimals="2"
      id="Fact_57cca4b8f1044664988a96c292d978d1"
      unitRef="U004">36.14</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
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      decimals="-5"
      id="Fact_87ca3f2ec59f473aaf7df5ff01d27232"
      unitRef="U001">72600000</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions>
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the PRSU activity for the year ended December 31, 2024 (in thousands, except per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Grant Date Fair&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2023&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;226&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56.04&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;179&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;78.41&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Vested&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(73&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.35&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;68.21&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;307&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;66.72&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes stock-based compensation expense for the years ended December 31, 2024, 2023 and 2022 (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cost of sales&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;767&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;499&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;533&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research, development and patent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;92,403&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,826&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;73,704&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;37,030&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,484&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,027&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation expense, net of amounts capitalized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,200&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105,809&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100,264&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Capitalized stock-based compensation expense&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;799&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total stock-based compensation expense&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,999&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105,809&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100,264&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.3 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.3 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.3 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Board of Director Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.5 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.7 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.4 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;ESPP:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;37.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;36.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;9. Income Taxes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Loss before income taxes is comprised of (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;United States&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(460,712&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(334,707&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(258,493&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;644&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;742&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;508&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Loss before income taxes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(460,068&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(333,965&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(257,985&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our income tax expense (benefit) was as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Current:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Federal&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,492&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;35,861&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,522&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(848&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,687&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,129&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;169&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;147&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total current income tax expense (benefit)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,171&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,321&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Federal&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total deferred income tax benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total income tax expense (benefit)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,171&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,321&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to loss before income taxes. The sources
    and tax effects of the differences are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="22" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Pre-tax loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(460,068&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(333,965&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(257,985&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Statutory rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(96,614&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(70,133&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(54,177&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State income tax net of federal benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,889&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(22,597&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13,622&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(22&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(49&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net change in valuation allowance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;152,590&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(33.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;175,388&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(52.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,951&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(40.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax credits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(53,497&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(67,131&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax rate change&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,815&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,091&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Non-deductible compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,895&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,814&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other non-deductible items&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;188&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;327&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign-derived intangible income benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21,071&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,493&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,732&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19,546&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,030&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;665&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(401&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;344&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,171&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,321&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred income taxes reflect the net tax effects of temporary differences between the carrying amounts of assets and liabilities for
    financial reporting purposes and the amounts used for income tax purposes.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Significant components of our deferred tax assets and liabilities as of December 31, 2024 and 2023 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred Tax Assets:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net operating loss carryovers&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;95,851&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,964&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax credits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;310,703&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;239,962&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,063&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,683&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;82,660&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,468&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Intangible and capital assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;93,541&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,380&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Convertible debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,310&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,849&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Capitalized research and development expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;323,560&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;238,738&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Long-term lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,481&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,718&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;148,918&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;144,608&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,343&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total deferred tax assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,174,111&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,025,713&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred Tax Liabilities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Fixed assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,719&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,166&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Right-of-use assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(36,788&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(42,007&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,896&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,910&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net deferred tax asset&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,129,708&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;977,630&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Valuation allowance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,129,708&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(977,630&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total net deferred tax assets and liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2024, we maintained a full valuation allowance on our net deferred tax assets. We determined the valuation allowance in
    accordance with the provisions of ASC 740, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Accounting for Income Taxes&lt;/span&gt;, which requires an assessment of both positive and negative evidence when
    determining whether it is more likely than not that deferred tax assets are realizable. Our recent history of cumulative losses and expected near-term future losses require us to record a full valuation allowance against all net deferred tax assets. We
    will maintain a full valuation allowance on net deferred tax assets until sufficient positive evidence exists to support reversal of the valuation allowance&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our valuation allowance increased by $152
    million from December 31, 2023 to December 31, 2024.
    The increase was primarily related to increases in our deferred tax assets for capitalized research and development expenses and tax credits.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2024, we had
    federal and state, primarily California, tax net operating loss carryforwards of $290.2 million and $526.9 million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2032. At December 31, 2024, we also had federal and California research and development tax credit carryforwards of $234.2 million and $137.6 million, respectively. Our federal research and
    development tax credit carryforwards will begin to expire in 2037. Our California research and development tax credit carryforwards are available indefinitely.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Utilization of the net operating loss and tax credit carryforwards may be subject to an annual limitation due to the ownership change
    limitations provided by the Internal Revenue Code of 1986, as amended, and similar state provisions. The annual limitation may result in the expiration of net operating losses and credits before utilization.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We analyze filing positions in all U.S. federal, state and foreign jurisdictions where we file income tax returns, and all open tax years
    in these jurisdictions to determine if we have any uncertain tax positions on any of our income tax returns. We recognize the impact of an uncertain tax position on an income tax return at the largest amount that the relevant taxing authority is
    more-likely-than not to sustain upon audit. We do not recognize uncertain income tax positions if they have less than 50 percent likelihood of the applicable tax authority sustaining our position.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes our gross unrecognized tax benefits &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(in thousands):&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning balance of unrecognized tax benefits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,298&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,567&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55,085&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Decrease for lapse of statute of limitations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,579&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14,993&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Decrease for prior period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(110&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(267&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Increase for prior period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,902&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;429&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;259&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Increase for current period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,650&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,032&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,490&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance of unrecognized tax benefits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,161&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,298&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,567&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in the balance of unrecognized tax benefits at December 31, 2024, 2023 and 2022 was $0.3 million, $0.3 million and $6.2 million respectively, that if we recognized, could
    impact our effective tax rate, subject to our remaining valuation allowance.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not expect any material changes to our gross unrecognized tax benefits within the next 12 months.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize interest and/or penalties related to income tax matters in income tax expense. During the years ended December 31, 2024, 2023 and 2022, we recognized $0.1 million, $0.1 million and $0.8 million, respectively, of
    accrued interest and penalties related to gross unrecognized tax benefits.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are subject to taxation in the U.S. and various state and
      foreign jurisdictions. U.S. tax years 2021 through 2023 remain open to examination and tax years 2020 through 2023 remain open to examination by major state taxing jurisdictions, primarily California, although net operating loss and credit
      carryforwards generated prior to these periods may still be adjusted upon examination by the Internal Revenue Service or state tax authorities if they have been used in an open period or are used in a future period&lt;/span&gt;.&lt;/div&gt;
</us-gaap:IncomeTaxDisclosureTextBlock>
    <us-gaap:ScheduleOfIncomeBeforeIncomeTaxDomesticAndForeignTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_7281bd0eb54443b994694c659a6a8f66">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Loss before income taxes is comprised of (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;United States&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(460,712&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(334,707&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(258,493&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;644&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;742&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;508&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Loss before income taxes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(460,068&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(333,965&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(257,985&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfIncomeBeforeIncomeTaxDomesticAndForeignTableTextBlock>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic
      contextRef="c20240101to20241231"
      decimals="-3"
      id="Fact_1154d9477ea5403c89bcaba61b591e79"
      unitRef="U001">-460712000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_74d3abad4f744e0aa68801acc3a6ed6b"
      unitRef="U001">-334707000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_8977ca2c8272434794efd8259c5f22b7"
      unitRef="U001">-258493000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20240101to20241231"
      decimals="-3"
      id="Fact_70ca994a31be49619caefe5e71de1587"
      unitRef="U001">644000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_8425f2adaf6948cdb4db61cdf7def1fc"
      unitRef="U001">742000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_15eeca6092a14a5c9b839eb716ea8ae4"
      unitRef="U001">508000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest
      contextRef="c20240101to20241231"
      decimals="-3"
      id="Fact_317564d38d3f4684aaa47f65a5d386e8"
      unitRef="U001">-460068000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_9fd05fd89e164623ad7d51c758cf30c6"
      unitRef="U001">-333965000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_225bd758b4d047a9b56b2a1266e8768e"
      unitRef="U001">-257985000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest>
    <us-gaap:ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_d123dff19b9e4823b03cc17efdea0755">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our income tax expense (benefit) was as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Current:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Federal&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,492&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;35,861&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,522&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(848&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,687&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,129&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;169&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;147&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total current income tax expense (benefit)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,171&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,321&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Federal&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total deferred income tax benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total income tax expense (benefit)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,171&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,321&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock>
    <us-gaap:CurrentFederalTaxExpenseBenefit
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    <us-gaap:CurrentFederalTaxExpenseBenefit
      contextRef="c20230101to20231231"
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to loss before income taxes. The sources
    and tax effects of the differences are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="22" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Pre-tax loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(460,068&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(333,965&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(257,985&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Statutory rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(96,614&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(70,133&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(54,177&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State income tax net of federal benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,889&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(22,597&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13,622&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(22&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(49&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net change in valuation allowance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;152,590&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(33.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;175,388&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(52.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,951&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(40.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax credits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(53,497&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(67,131&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax rate change&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,815&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,091&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Non-deductible compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,895&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,814&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other non-deductible items&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;188&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;327&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign-derived intangible income benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21,071&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,493&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,732&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19,546&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,030&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;665&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(401&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;344&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective rate&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,171&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,321&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9.7&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4.5&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Significant components of our deferred tax assets and liabilities as of December 31, 2024 and 2023 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred Tax Assets:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net operating loss carryovers&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;95,851&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,964&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax credits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;310,703&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;239,962&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,063&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,683&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;82,660&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,468&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Intangible and capital assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;93,541&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,380&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Convertible debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,310&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,849&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Capitalized research and development expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;323,560&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;238,738&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Long-term lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,481&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,718&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;148,918&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;144,608&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,343&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total deferred tax assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,174,111&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,025,713&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred Tax Liabilities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Fixed assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,719&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,166&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Right-of-use assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(36,788&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(42,007&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,896&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,910&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net deferred tax asset&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,129,708&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;977,630&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Valuation allowance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,129,708&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(977,630&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total net deferred tax assets and liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes our gross unrecognized tax benefits &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(in thousands):&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning balance of unrecognized tax benefits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,298&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,567&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55,085&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Decrease for lapse of statute of limitations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,579&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14,993&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Decrease for prior period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(110&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(267&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Increase for prior period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,902&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;429&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;259&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Increase for current period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,650&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,032&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,490&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance of unrecognized tax benefits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,161&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,298&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,567&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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      contextRef="c20221231"
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      contextRef="c20211231"
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      unitRef="U001">7579000</us-gaap:UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations>
    <us-gaap:UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations
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      unitRef="U001">14993000</us-gaap:UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations>
    <us-gaap:UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations
      contextRef="c20220101to20221231"
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      id="Fact_6152a6544b8f4685b14436ee97f6ce58"
      unitRef="U001">0</us-gaap:UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations>
    <us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions
      contextRef="c20240101to20241231"
      decimals="-3"
      id="Fact_3f06e5d0f5b747c280280e9fcf69a448"
      unitRef="U001">110000</us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions>
    <us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_39287cd4b49c44a4a617144fa53df1bf"
      unitRef="U001">737000</us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions>
    <us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_0bb19795798b4cca8d22978a26340bd0"
      unitRef="U001">267000</us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions>
    <us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions
      contextRef="c20240101to20241231"
      decimals="-3"
      id="Fact_ecf1724d9d65437ab5ccd486d8ab6ebd"
      unitRef="U001">1902000</us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions>
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      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_0ad407c0955648c48850ba2d8d052462"
      unitRef="U001">429000</us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions>
    <us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_7d0ea3f6a325421b85ab3cbb04eb12fa"
      unitRef="U001">259000</us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions>
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      contextRef="c20240101to20241231"
      decimals="-3"
      id="Fact_6119186f5d854118b836ddc5c481ef2d"
      unitRef="U001">3650000</us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions>
    <us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_f3e7b13433a84e72a642c54ecc6a02b3"
      unitRef="U001">2032000</us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions>
    <us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_809af95107674a60b9a6aa50165e5ba7"
      unitRef="U001">1490000</us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions>
    <us-gaap:UnrecognizedTaxBenefits
      contextRef="c20241231"
      decimals="-3"
      id="Fact_c2747640a25a483791181f56caf8bc45"
      unitRef="U001">41161000</us-gaap:UnrecognizedTaxBenefits>
    <us-gaap:UnrecognizedTaxBenefits
      contextRef="c20231231"
      decimals="-3"
      id="Fact_58382ea6463045ef8f7cefb3fdbf3dd7"
      unitRef="U001">43298000</us-gaap:UnrecognizedTaxBenefits>
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      contextRef="c20221231"
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      id="Fact_ed1574437d194d92b955e24fdec9efce"
      unitRef="U001">56567000</us-gaap:UnrecognizedTaxBenefits>
    <us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate
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      id="Fact_552285171ef248dfab36d0ee9948271e"
      unitRef="U001">300000</us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate>
    <us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate
      contextRef="c20231231"
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      contextRef="c20221231"
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      unitRef="U001">6200000</us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate>
    <us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense
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      id="Fact_5d817f0050924f7f82257fc7b70a23d7"
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    <us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense
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    <us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense
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      decimals="-5"
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    <us-gaap:PensionAndOtherPostretirementBenefitsDisclosureTextBlock
      contextRef="c20240101to20241231"
      id="Text_44a1974bfba9485682c02d2913778f03">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;10. Employment Benefits&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have employee 401(k) salary deferral plans covering all employees. Employees could make contributions by withholding a percentage of
    their salary up to the IRS annual limits of $23,000 and $30,500 in 2024 for employees under 50 years old and employees 50 years old or over, respectively. We made
    approximately $8.6 million, $7.1
    million and $5.6 million in matching contributions for the years ended December 31, 2024, 2023 and 2022, respectively.&lt;/div&gt;
</us-gaap:PensionAndOtherPostretirementBenefitsDisclosureTextBlock>
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      unitRef="U001">23000</us-gaap:DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount>
    <us-gaap:DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount
      contextRef="c20240101to20241231_RangeAxis_MaximumMember"
      decimals="0"
      id="Fact_2703ad6213db4e249c38d0794a2c6418"
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    <us-gaap:DefinedContributionPlanCostRecognized
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      decimals="-5"
      id="Fact_345fd7748408424580894d7cb0e0e108"
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    <us-gaap:DefinedContributionPlanCostRecognized
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      decimals="-5"
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      unitRef="U001">7100000</us-gaap:DefinedContributionPlanCostRecognized>
    <us-gaap:DefinedContributionPlanCostRecognized
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      decimals="-5"
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    <us-gaap:LegalMattersAndContingenciesTextBlock
      contextRef="c20240101to20241231"
      id="Text_656730b2a28e4e958b751e639ff66fd5">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;11. Legal Proceedings&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the
    status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of
    any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the
    amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;There are no pending material legal proceedings to which we are a party or of which our property is the subject.&lt;/div&gt;
</us-gaap:LegalMattersAndContingenciesTextBlock>
    <us-gaap:SegmentReportingDisclosureTextBlock
      contextRef="c20240101to20241231"
      id="Text_fbf9a7cc665b405c8fc8a906a61d8c8c">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;12. Segment Information&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We operate as a &lt;span style="-sec-ix-hidden:Fact_2519ca12728c45f9b7af0ac92fa19388"&gt;single&lt;/span&gt;
    operating segment, Ionis operations, focused on the research, development and commercialization of our RNA-targeted medicines to bring better futures to people with serious diseases. As the CODM, our Chief Executive Officer manages our company, reviews
    operating results, assesses performance and allocates resources on an aggregate basis using consolidated net income or loss as the key measure of segment profit or loss. As such, results of our operations are reported on a consolidated basis for
    purposes of management and segment reporting.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis operations derives its revenues from commercial and R&amp;amp;D revenue sources. Refer to Note 3, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Revenues&lt;/span&gt;, for further details on our sources of revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table sets forth information on segment profit or loss, including significant segment expenses (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;705,138&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;787,647&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;587,367&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cost of sales&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,415&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,686&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13,447&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Drug discovery&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;114,350&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;125,649&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;181,302&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Drug development&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;527,259&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;530,332&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;426,225&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Medical affairs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,229&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19,454&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,948&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Manufacturing and development chemistry&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,293&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76,162&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D support&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;82,559&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;81,019&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59,840&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;230,478&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;205,135&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;124,370&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other segment items (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;109,016&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;118,365&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(40,205&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Consolidated net loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(453,897&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(366,286&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(269,722&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other segment items include stock-based compensation expense, investment income, interest expense, gain or loss on investments, other income or expense and income tax expense or benefit.&#160;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:SegmentReportingDisclosureTextBlock>
    <us-gaap:ScheduleOfSegmentReportingInformationBySegmentTextBlock
      contextRef="c20240101to20241231"
      id="Text_b2b561d49309464381e5b50edeb230c5">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table sets forth information on segment profit or loss, including significant segment expenses (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt; &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;705,138&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;787,647&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;587,367&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cost of sales&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,415&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,686&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13,447&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Drug discovery&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;114,350&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;125,649&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;181,302&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Drug development&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;527,259&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;530,332&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;426,225&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Medical affairs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,229&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19,454&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,948&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Manufacturing and development chemistry&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,293&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76,162&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D support&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;82,559&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;81,019&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59,840&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;230,478&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;205,135&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;124,370&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other segment items (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;109,016&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;118,365&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(40,205&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(453,897&lt;/div&gt;
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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(366,286&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(269,722&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

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  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other segment items include stock-based compensation expense, investment income, interest expense, gain or loss on investments, other income or expense and income tax expense or benefit.&#160;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;13. Fourth Quarter Financial Data (Unaudited)&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following financial information reflects all normal recurring adjustments, which are, in the opinion of management, necessary for a
    fair statement of the results of the interim periods. Summarized fourth quarter data for 2024 and 2023 are as follows (in thousands, except per share data).&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;226,577&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;324,505&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating expenses (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;337,398&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;330,627&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Loss from operations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(110,821&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,122&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(104,349&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share (3) (4)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.66&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.06&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Diluted net loss per share (3) (5)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.66&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.06&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Revenue was lower in the three months ended December 31, 2024 compared to the same period in 2023 primarily due to significant partner payments earned in the fourth quarter of 2023, including the $&lt;/span&gt;50&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone payment we earned from AstraZeneca when the FDA
              approved WAINUA for ATTRv-PN in the U.S., $&lt;/span&gt;36&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;
              million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis. &lt;/span&gt;In addition, WAINUA
            joint development revenue decreased in the three months ended December 31, 2024 compared to the same period in 2023 as development activities relating to ATTRv-PN wound down with the launch of WAINUA.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating expenses were relatively consistent in the three months
            ended December 31, 2024 compared to the same period in 2023.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We &lt;/span&gt;compute net loss per share independently for each quarter during &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;the year.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As discussed in Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and Significant Accounting Policies, &lt;/span&gt;we compute basic net loss per share by dividing the total net loss by our weighted-average number of common shares outstanding
            during the period.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We incurred a net loss for the fourth quarter of 2024 and 2023. As a
            result, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:QuarterlyFinancialInformationTextBlock>
    <us-gaap:ScheduleOfQuarterlyFinancialInformationTableTextBlock
      contextRef="c20240101to20241231"
      id="Text_53a7dc3cb94e432bbe1ab7ec6da16d34">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following financial information reflects all normal recurring adjustments, which are, in the opinion of management, necessary for a
    fair statement of the results of the interim periods. Summarized fourth quarter data for 2024 and 2023 are as follows (in thousands, except per share data).&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;226,577&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;324,505&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating expenses (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;337,398&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;330,627&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Loss from operations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(110,821&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,122&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(104,349&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share (3) (4)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.66&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.06&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Diluted net loss per share (3) (5)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.66&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.06&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Revenue was lower in the three months ended December 31, 2024 compared to the same period in 2023 primarily due to significant partner payments earned in the fourth quarter of 2023, including the $&lt;/span&gt;50&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone payment we earned from AstraZeneca when the FDA
              approved WAINUA for ATTRv-PN in the U.S., $&lt;/span&gt;36&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;
              million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis. &lt;/span&gt;In addition, WAINUA
            joint development revenue decreased in the three months ended December 31, 2024 compared to the same period in 2023 as development activities relating to ATTRv-PN wound down with the launch of WAINUA.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating expenses were relatively consistent in the three months
            ended December 31, 2024 compared to the same period in 2023.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We &lt;/span&gt;compute net loss per share independently for each quarter during &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;the year.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As discussed in Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and Significant Accounting Policies, &lt;/span&gt;we compute basic net loss per share by dividing the total net loss by our weighted-average number of common shares outstanding
            during the period.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000; border-spacing: 0;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We incurred a net loss for the fourth quarter of 2024 and 2023. As a
            result, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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